Histone deacetylase inhibitors and their use

Abstract

The objective is to provide a histone deacetylase inhibitor and its use. [Solution] The present invention relates to histone deacetylase inhibitors and their use, and belongs to the field of chemical technology. In this invention, a structurally novel and highly efficient HDACs inhibitor is obtained by introducing a succinimide fragment. An advantageous effect of the present invention is that these compounds exhibit excellent inhibitory activity against HDACs and also have excellent in vitro antitumor activity, providing a new means for the application of HDAC inhibitors to solid tumors or for the treatment of diseases associated with abnormalities in histone deacetylase activity.

Description

[Technical Field]

[0001] The present invention relates to a histone deacetylase inhibitor and its use, and belongs to the field of chemical technology. [Background technology]

[0002] Epigenetic abnormalities are closely associated with the development of many human diseases and are primarily caused by dysfunction of epigenetic proteins resulting from gene deficiencies. Histone deacetylases (HDACs) and histone acetyltransferases (HATs) are enzymes with opposing biological functions that dynamically regulate histone deacetylation and acetylation. In normal cells, HDACs and HATs maintain a dynamic balance and play a crucial role in the normal expression of genes. However, this dynamic balance between HDACs and HATs is disrupted by abnormally increased biological activity of HDACs, leading to abnormal expression of genes involved in the cell cycle and apoptosis, as well as abnormalities in related signaling pathways. Studies have shown that abnormal HDAC expression is closely associated with the development and progression of a variety of diseases, including cancer, inflammatory diseases, and neurological disorders. For this reason, the development of HDAC inhibitors is attracting widespread interest in the field of pharmaceutical development and has enormous potential for application. To date, the U.S. Food and Drug Administration has sequentially approved four HDAC inhibitors: vorinostat, romidepsin, bellinostat, and panobinostat. The China Food and Drug Administration has also approved tidamide. These are primarily used to treat hematopoietic malignancies such as cutaneous T-cell lymphoma, peripheral T-cell lymphoma, and multiple myeloma. However, HDAC inhibitors face significant bottlenecks and challenges. While currently marketed HDAC inhibitors show good therapeutic results in the treatment of hematopoietic malignancies, their efficacy as monotherapy against solid tumors such as breast cancer, kidney cancer, prostate cancer, and head and neck cancer is generally poor, limiting their clinical application. Therefore, there is an urgent clinical need to develop HDAC inhibitors with novel structures and high activity to expand their applicability to solid tumors. [Overview of the project] [Problems that the invention aims to solve]

[0003] In view of the drawback that existing HDAC inhibitors in the prior art do not show sufficient therapeutic effect against solid tumors, this invention aims to develop a new histone deacetylase inhibitor, and to provide a more efficient and safer HDAC inhibitor, thereby improving the therapeutic effect of HDAC inhibitors against solid tumors. [Means for solving the problem]

[0004] HDAC small molecule inhibitors are primarily composed of four parts: a zinc ion binding group (ZBG), a linker, a connect unit (CU), and a cap group (Cap). Prior research on HDAC small molecule inhibitors has mainly focused on the zinc ion binding group and the connect unit, with the CU in most HDAC inhibitors being a simple sp group such as an amide or carbonyl group. 2 They are often hybrid groups. However, CU has an extremely important influence on molecular structure, and even on pharmacokinetic properties. Therefore, the object of the present invention is to provide novel and effective HDACs inhibitors and pharmaceutically acceptable salts thereof. To this end, the present invention first provides compounds represented by the following general formula.

[0005] [ka] (In the formula, X, Y, Z, M 1 M 2 Each of these independently represents a carbon atom or a nitrogen atom. X, Y, XX, M 1 M 2 If is a carbon atom, then independently, R 2 It may be arbitrarily substituted with R 2is hydrogen, an alkyl group, a cyano group, a halogen, a haloalkyl group, a hydroxy group, a mercapto group, an alkoxy group, an alkylamino group, an alkylthio group, an alkoxyalkyl group, an arylalkyl group, a diarylalkyl group, an aryl group or Het, M 3 is carbon, and each R 4 、R 5 may be optionally substituted with, and R 4 、R 5 is hydrogen, deuterium, an alkyl group, a haloalkyl group, a hydroxy group, a mercapto group, an alkoxy group, an alkylamino group, an alkylthio group, an alkoxyalkyl group, methylene, an arylalkyl group, a diarylalkyl group, an aryl group or Het, Q 1 is selected from a saturated or unsaturated straight-chain or branched-chain hydrocarbon group having 1 to 8 carbon atoms, an aryl group or Het, R 1 is a hydroxy group, a 2-aminophenyl group substituted with one or more R 3 groups, R 3 is hydrogen, an alkyl group, a cyano group, a halogen, a haloalkyl group, a hydroxy group, a mercapto group, an alkoxy group, an alkylthio group, an alkoxyalkyl group, an arylalkyl group, an aryl group or Het, The alkyl group is a straight-chain or branched-chain saturated hydrocarbon group having 1 to 6 carbon atoms, or a cyclic saturated hydrocarbon group having 3 to 6 carbon atoms, or a cyclic saturated hydrocarbon group having 3 to 6 carbon atoms bonded to a straight-chain or branched-chain saturated hydrocarbon group having 1 to 6 carbon atoms, The alkoxy group is a straight-chain or branched-chain saturated hydrocarbon group having 1 to 6 carbon atoms, or a cyclic saturated hydrocarbon group having 3 to 6 carbon atoms, or a cyclic saturated hydrocarbon group having 3 to 6 carbon atoms bonded to a straight-chain or branched-chain saturated hydrocarbon group having 1 to 6 carbon atoms, and each carbon atom may be optionally substituted with oxygen, The alkylamino group is a linear or branched saturated hydrocarbon group having 1 to 6 carbon atoms, or a cyclic saturated hydrocarbon group having 3 to 6 carbon atoms, or a cyclic saturated hydrocarbon group having 3 to 6 carbon atoms bonded to a linear or branched saturated hydrocarbon group having 1 to 6 carbon atoms, and each carbon atom may be optionally substituted with an NH group. An alkoxyalkyl group is a group formed by the bonding of an alkoxy group and an alkyl group as defined above. Alkenyl and alkynyl groups are linear or branched unsaturated hydrocarbon groups having 1 to 6 carbon atoms, and containing double or triple bonds. The aryl group is a carbon ring selected from a phenyl group, a naphthyl group, an acenaphthyl group, or a tetrahydronaphthyl group, each of which may be optionally substituted with one, two, or three substituents, each substituent independently selected from hydrogen, alkyl, cyano, halogen, haloalkyl, hydroxy, mercapto, alkoxy, alkylthio, alkoxyalkyl, arylalkyl, diarylalkyl, aryl, or Het. Arylalkyl groups and diarylalkyl groups are groups formed by bonding an aryl group and an alkyl group as defined above. It is a group selected from a monocyclic heterocyclic ring selected from a pyrrolyl group, a pyrazolyl group, an imidazolyl group, a furanyl group, a thienyl group, an oxazolyl group, an isoxazolyl group, a thiazolyl group, an isothiazolyl group, a pyridyl group, a pyrimidyl group, a pyrazinyl group or a pyridazinyl group, or a bicyclic heterocyclic ring selected from a quinolinyl group, a quinoxalinyl group, an indolyl group, a benzimidazolyl group, a benzoxazolyl group, a benzoisoxazolyl group, a benzothiazolyl group, a benzoisothiazolyl group, a benzofuranyl group, a benzothienyl group, 2,3-dihydrobenzo[1,4]dioxacyclohexenyl, or benzo[1,3]dioxacyclopentenyl, or a monocyclic saturated hydrocarbon group having 3 to 6 carbon atoms or a bicyclic saturated hydrocarbon group having 6 to 12 carbon atoms, and the carbon atoms on the ring may be independently and optionally substituted with 1 to 4 O, S, N or NH, and each monocyclic or bicyclic ring may be optionally substituted with 1, 2 or 3 substituents, and each substituent is independently selected from halogen, haloalkyl, hydroxy, alkyl or alkoxy, Halogen is a substituent selected from fluorine, chlorine, bromine or iodine, The haloalkyl group is a linear or branched saturated hydrocarbon group having 1 to 6 carbon atoms, or a cyclic saturated hydrocarbon group having 3 to 6 carbon atoms, or a cyclic saturated hydrocarbon group having 3 to 6 carbon atoms bonded to a linear or branched saturated hydrocarbon group having 1 to 6 carbon atoms, and one or more carbon atoms may be substituted with one or more halogen atoms.)

[0006] The present invention further selects the following compounds as HDACs inhibitors. In the formula, X, Y, Z, M 1 , M 2 each independently represents a carbon atom or a nitrogen atom, and when X, Y, Z, M 1 , M 2 are carbon atoms, they may each independently be optionally substituted with R 2 , and R 2 is hydrogen, an alkyl group, a cyano group, a halogen, a haloalkyl group, an alkoxy group, an alkylthio group, an alkoxyalkyl group, M 3is carbon, and each is independently R 4 、R 5 may be optionally substituted with, R 4 、R 5 is hydrogen, deuterium, alkyl, haloalkyl group, hydroxy group, mercapto group, alkoxy group, alkylamino group, alkylthio group, alkoxyalkyl group, methylene, arylalkyl group, diarylalkyl group, aryl group or Het, Q 1 is selected from a saturated or unsaturated straight-chain or branched-chain hydrocarbon group having 1 to 8 carbon atoms, an aryl group, R 1 is selected from a hydroxy group, a 2-aminophenyl group substituted with one or more R 3 、 R 3 is hydrogen, alkyl group, cyano group, halogen, haloalkyl group, aryl group or Het.

[0007] The present invention further selects the following compounds as HDACs inhibitors. In the formula, X, Y, Z, M 1 、M 2 each independently represents a carbon atom or a nitrogen atom, and when X, Y, Z, M 1 、M 2 are carbon atoms, each may be optionally substituted with R 2 、R 2 is hydrogen, alkyl, halogen, alkoxy group, M 3 is carbon, and each is independently R 4 、R 5 may be optionally substituted with, R 4 、R 5 is hydrogen, deuterium, alkyl group, haloalkyl group, hydroxy group, mercapto group, alkoxy group, alkylamino group, alkylthio group, alkoxyalkyl group, methylene, arylalkyl group, diarylalkyl group, aryl group or Het, Q 1 is selected from a saturated or unsaturated straight-chain or branched-chain hydrocarbon group having 3 to 8 carbon atoms, an aryl group, R1 is a hydroxyl group, one or more R 3 Selected from substituted 2-aminophenyl groups, R 3 This is hydrogen, alkyl group, cyano group, halogen, haloalkyl group, aryl group, or Het.

[0008] The present invention further selects the following compounds as HDACs inhibitors. (E)-4-(3-benzylidene-2,5-dioxopyrrolidinyl)-N-hydroxybutylamide(I-1), (E)-4-(3-benzylidene-2,5-dioxopyrrolidinyl)-N-hydroxypentylamide(I-2), (E)-4-(3-benzylidene-2,5-dioxopyrrolidinyl)-N-hydroxyhexylamide(I-3), (E)-4-(3-benzylidene-2,5-dioxopyrrolidinyl)-N-hydroxyheptylamide(I-4), (E)-4-(3-benzylidene-2,5-dioxopyrrolidinyl)-N-hydroxyoctylamide(I-5), (E)-N-(2-amino-4-fluorophenyl)-4-(3-benzylidene-2,5-dioxopyrrolidinyl)butylamide(I-6), (E)-N-(2-amino-4-fluorophenyl)-5-(3-benzylidene-2,5-dioxopyrrolidinyl)pentylamide (I-7), (E)-N-(2-amino-4-fluorophenyl)-6-(3-benzylidene-2,5-dioxopyrrolidinyl)hexylamide(I-8), (E)-N-(2-amino-4-fluorophenyl)-7-(3-benzylidene-2,5-dioxopyrrolidinyl)heptylamide(I-9), 4-(3-((E)-benzylidene)-2,5-dioxopyrrolidinyl)-N-((1S,2S)-2-hydroxycyclohexyl)butylamide(I-10), 5-(3-((E)-benzylidene)-2,5-dioxopyrrolidinyl)-N-((1S,2S)-2-hydroxycyclohexyl)pentylamide (I-11), 6-(3-((E)-benzylidene)-2,5-dioxopyrrolidinyl)-N-((1S,2S)-2-hydroxycyclohexyl)hexylamide(I-12), 7-(3-((E)-benzylidene)-2,5-dioxopyrrolidinyl)-N-((1S,2S)-2-hydroxycyclohexyl)heptylamide (I-13), 8-(3-((E)-benzylidene)-2,5-dioxopyrrolidinyl)-N-((1S,2S)-2-hydroxycyclohexyl)octylamide(I-14), (E)-7-(3-(4-isopropylbenzylidene)-2,5-dioxopyrrolidinyl)-N-hydroxyheptylamide(I-15), (E)-7-(3-(4-dimethylaminobenzylidene)-2,5-dioxopyrrolidinyl)-N-hydroxyheptylamide(I-16), (E)-7-(3-(4-trifluoromethylbenzylidene)-2,5-dioxopyrrolidinyl)-N-hydroxyheptylamide(I-17), (E)-7-(3-(4-methylbenzylidene)-2,5-dioxopyrrolidinyl)-N-hydroxyheptylamide(I-18), (E)-7-(3-(2-methylbenzylidene)-2,5-dioxopyrrolidinyl)-N-hydroxyheptylamide(I-19), (E)-7-(3-(2-cyanobenzylidene)-2,5-dioxopyrrolidinyl)-N-hydroxyheptylamide (I-20), (E)-7-(3-(2-pyridylmethylidene)-2,5-dioxopyrrolidinyl)-N-hydroxyheptylamide (I-21), (E)-7-(3-(2-naphthylmethylidene)-2,5-dioxopyrrolidinyl)-N-hydroxyheptylamide(I-22), (E)-7-(3-(2-thienylmethylidene)-2,5-dioxopyrrolidinyl)-N-hydroxyheptylamide (I-23), (E)-7-(3-(2-chlorobenzylidene)-2,5-dioxopyrrolidinyl)-N-hydroxyheptylamide(I-24), (E)-7-(3-(3-chlorobenzylidene)-2,5-dioxopyrrolidinyl)-N-hydroxyheptylamide(I-25), (E)-7-(3-(4-chlorobenzylidene)-2,5-dioxopyrrolidinyl)-N-hydroxyheptylamide(I-26), (E)-7-(3-(3-bromobenzylidene)-2,5-dioxopyrrolidinyl)-N-hydroxyheptylamide (I-27), (E)-7-(3-(3-fluorobenzylidene)-2,5-dioxopyrrolidinyl)-N-hydroxyheptylamide(I-28), (E)-7-(3-(3-iodobenzylidene)-2,5-dioxopyrrolidinyl)-N-hydroxyheptylamide (I-29), (E)-7-(3-(3,4-dichlorobenzylidene)-2,5-dioxopyrrolidinyl)-N-hydroxyheptylamide (I-30), (E)-7-(3-(2-methoxybenzylidene)-2,5-dioxopyrrolidinyl)-N-hydroxyheptylamide (I-31), (E)-7-(3-(3-methoxybenzylidene)-2,5-dioxopyrrolidinyl)-N-hydroxyheptylamide(I-32), (E)-7-(3-(4-methoxybenzylidene)-2,5-dioxopyrrolidinyl)-N-hydroxyheptylamide (I-33), (E)-7-(3-(3,4-dimethoxybenzylidene)-2,5-dioxopyrrolidinyl)-N-hydroxyheptylamide (I-34), (E)-7-(3-(3,4,5-trimethoxybenzylidene)-2,5-dioxopyrrolidinyl)-N-hydroxyheptylamide(I-35), (E)-7-(3-(4-hydroxy-3,5-dimethoxybenzylidene)-2,5-dioxopyrrolidinyl)-N-hydroxyheptylamide (I-36), (E)-7-(3-(2-hydroxybenzylidene)-2,5-dioxopyrrolidinyl)-N-hydroxyheptylamide(I-37), (E)-7-(3-(2-ethoxybenzylidene)-2,5-dioxopyrrolidinyl)-N-hydroxyheptylamide(I-38), (E)-7-(3-(5-bromo-2-methoxybenzylidene)-2,5-dioxopyrrolidinyl)-N-hydroxyheptylamide (I-39), (E)-7-(3-(4-bromo-2-methoxybenzylidene)-2,5-dioxopyrrolidinyl)-N-hydroxyheptylamide (I-40), (E)-4-((3-benzylidene-2,5-dioxopyrrolidinyl)methyl)-N-hydroxybenzoylamide(I-41)

[0009] The above-mentioned compounds are prepared by the following method.

[0010] [ka]

[0011] The compounds of the present invention can be prepared by the method described above or a similar method, and appropriate starting materials should be selected depending on the type and substitution position of the substituents.

[0012] The present invention further provides a pharmaceutical composition comprising the above compound or a pharmaceutically acceptable salt thereof and a pharmaceutically acceptable carrier. In the pharmaceutical composition, the above compound or a pharmaceutically acceptable salt thereof is the active ingredient.

[0013] The present invention further provides the use of the above compounds in the preparation of pharmaceuticals used for the prevention or treatment of clinical symptoms associated with HDACs. Hereinafter, diseases associated with HDACs include lung cancer, melanoma, liver cancer, kidney cancer, leukemia, prostate cancer, thyroid cancer, skin diseases, pancreatic cancer, ovarian cancer, testicular cancer, breast cancer, bladder cancer, gallbladder cancer, myelodysplastic syndrome, lymphoma, esophageal cancer, gastrointestinal cancer, astrocytoma, neuroblastoma, glioma, schwannoma, mesothelioma, non-insulin-dependent diabetes mellitus, and autoimmune diseases. [Effects of the Invention]

[0014] In this invention, a novel and highly efficient HDAC inhibitor is obtained by cyclizing an amide bond (CU) to form a five-membered ring. The advantageous effect of this invention is that it exhibits excellent inhibitory activity against HDACs, as well as excellent in vitro antitumor activity, providing a new direction for research into the application of HDAC inhibitors to solid tumors. [Modes for carrying out the invention]

[0015] (Example 1) (E)-4-(3-benzylidene-2,5-dioxopyrrolidinyl)-N-hydroxybutylamide(I-1)

[0016] [ka]

[0017] Step a: Synthesis of (E)-3-benzylidenepyrrolidine-2,5-dione In a 100 mL round-bottom flask, maleimide (5 mmol, 485.35 mg), methanol (10 mL), triphenylphosphine (6 mmol, 1.57 g), and benzaldehyde (7.5 mmol, 795 mg) were added sequentially, and the mixture was reacted at 60°C under reflux and stirring for 8 hours. When the reaction solution was cooled to room temperature, a solid precipitated, which was then filtered by suction, and the filtered cake was dried to obtain 750 mg of a white solid (yield 80.1%). 1H NMR (400 MHz, DMSO-d6) δ 11.45 (s, 1H), 7.66 - 7.59 (m, 2H), 7.52 - 7.41 (m, 3H), 7.39 (t, J = 2.5 Hz, 1H), 3.66 (d, J = 2.5 Hz, 2H).

[0018] Step b: Synthesis of ethyl (E)-4-(3-benzylidene-2,5-dioxopyrrolidinyl)butanoate (E)-3-benzylidenepyrrolidine-2,5-dione (749 mg, 4 mmol), DMF (10 mL), and potassium carbonate (829 mg, 6 mmol) were sequentially added to a 100 mL round-bottom flask and stirred under an ice bath for 30 minutes. After removing the ice bath and allowing the reaction mixture to return to room temperature, ethyl butanoate bromide (1.56 g, 8 mmol) was added and stirred at room temperature for 8 hours. The reaction mixture was extracted with water and ethyl acetate, and the organic layer was concentrated. Elution was performed by column chromatography using petroleum ether / ethyl acetate (volume ratio 3:1) as the eluent to obtain 678 mg of a clear liquid (yield 56.2%). 1H NMR (300 MHz, Chloroform-d) δ 7.71 - 7.36 (m, 6H), 4.13 (q, J = 7.1 Hz, 2H), 3.70 (t, J = 6.9 Hz, 2H), 3.57 (d, J = 2.4 Hz, 2H), 2.36 (t, J = 7.4 Hz, 2H), 1.99 (p, J = 7.2 Hz, 2H), 1.26 (t, J = 7.1 Hz, 3H).

[0019] Step c: Synthesis of (E)-4-(3-benzylidene-2,5-dioxopyrrolidinyl)-N-hydroxybutylamide In a 50 mL round-bottom flask, ethyl (E)-4-(3-benzylidene-2,5-dioxopyrrolidinyl)butanoate (600 mg, 1.99 mmol), glacial acetic acid (3 mL), and concentrated hydrochloric acid (0.5 mL) were added and stirred at 90°C. After confirming the completion of the reaction by TLC, the reaction solution was cooled, and water was added, causing a solid precipitate. The solution was then filtered, the filter cake was collected, and dried.

[0020] In a 50 mL round-bottom flask, the dry filter cake was added and dissolved in tetrahydrofuran (5 mL). Then, N,N'-carbonyldiimidazole (484 mg) was added and the mixture was stirred while reacting. After 1 hour, hydroxylamine hydrochloride (415 mg, 5.97 mmol) was gradually added, and the mixture was stirred for 12 hours. The reaction mixture was concentrated, and eluted by column chromatography using dichloromethane / methanol (volume ratio 25:1) as the eluent, yielding 63 mg of a pale yellow solid (yield 11%). 1H NMR (400 MHz, DMSO-d6) δ 10.36 (s, 1H), 8.71 (s, 1H), 7.69 - 7.62 (m, 2H), 7.48 (qt, J = 6.9, 3.7 Hz, 5H), 3.70 (d, J = 2.4 Hz, 2H), 3.50 (t, J = 7.1 Hz, 2H), 2.03 - 1.94 (m, 2H), 1.76 (p, J = 7.5 Hz, 2H).13C NMR (101 MHz, DMSO-d6) δ 174.78, 171.15, 168.83, 134.60, 132.37, 130.70, 130.27, 129.46, 125.80, 38.29, 34.20, 30.28, 24.05.

[0021] (Example 2) (E)-4-(3-benzylidene-2,5-dioxopyrrolidinyl)-N-hydroxypentylamide(I-2)

[0022] [ka]

[0023] Step a: Synthesis of (E)-3-benzylidenepyrrolidine-2,5-dione The operation and input amounts are the same as in step a of Example 1.

[0024] Step b: Synthesis of ethyl (E)-5-(3-benzylidene-2,5-dioxopyrrolidinyl)valerate The target compound was synthesized using ethyl bromide valerate as a raw material, in the same manner as in step b of Example 1.

[0025] Step c: Synthesis of (E)-5-(3-benzylidene-2,5-dioxopyrrolidinyl)-N-hydroxypentylamide (E)-5-(3-benzylidene-2,5-dioxopyrrolidinyl) ethyl valerate was used as a starting material, and the target compound was synthesized in the same manner as in step c of Example 1. A white solid was obtained (yield 15.2%). 1H NMR (400 MHz, DMSO-d6) δ 10.36 (s, 1H), 8.71 (s, 1H), 7.69 - 7.61 (m, 2H), 7.53 - 7.40 (m, 4H), 3.72 (d, J = 2.4 Hz, 2H), 3.48 (t, J = 6.2 Hz, 2H), 1.97 (t, J = 6.6 Hz, 2H), 1.58 - 1.48 (m, 2H), 1.51 - 1.41 (m, 2H). 13C NMR (101 MHz, DMSO) δ 174.80, 171.16, 169.23, 134.59, 132.42, 130.71, 130.28, 129.45, 125.74, 38.29, 34.15, 32.28, 27.44, 23.00.

[0026] (Example 3) (E)-4-(3-benzylidene-2,5-dioxopyrrolidinyl)-N-hydroxyhexylamide(I-3)

[0027] [ka]

[0028] Step a: Synthesis of (E)-3-benzylidenepyrrolidine-2,5-dione The operation and input amounts are the same as in step a of Example 1.

[0029] Step b: Synthesis of ethyl (E)-6-(3-benzylidene-2,5-dioxopyrrolidinyl)hexanoate The target compound was synthesized using ethyl bromide hexanoate as a raw material, in the same manner as in step b of Example 1.

[0030] Step c: Synthesis of (E)-6-(3-benzylidene-2,5-dioxopyrrolidinyl)-N-hydroxyhexylamide (E)-6-(3-benzylidene-2,5-dioxopyrrolidinyl)hexanoate ethyl was used as a starting material, and the target compound was synthesized in the same manner as in step c of Example 1. A yellow solid was obtained (yield 18.2%). 1H NMR (400 MHz, DMSO-d6) δ 10.33 (s, 1H), 8.66 (s, 1H), 7.69 - 7.62 (m, 2H), 7.56 - 7.40 (m, 4H), 3.72 (d, J = 2.4 Hz, 2H), 3.48 (t, J = 7.2 Hz, 2H), 1.94 (t, J = 7.4 Hz, 2H), 1.52 (dqd, J = 15.6, 7.7, 0.0 Hz, 4H), 1.31 - 1.17 (m, 2H). 13C NMR (101 MHz, DMSO) δ 174.79, 171.15, 169.45, 134.58, 132.40, 130.70, 130.28, 129.45, 125.74, 38.43, 34.14, 32.52, 27.57, 26.33, 25.18.

[0031] (Example 4) (E)-4-(3-benzylidene-2,5-dioxopyrrolidinyl)-N-hydroxyheptylamide(I-4)

[0032] [ka]

[0033] Step a: Synthesis of (E)-3-benzylidenepyrrolidine-2,5-dione The operation and input amounts are the same as in step a of Example 1.

[0034] Step b: Synthesis of ethyl (E)-7-(3-benzylidene-2,5-dioxopyrrolidinyl)heptanoate The target compound was synthesized using ethyl heptanoate bromide as a raw material, in the same manner as in step b of Example 1.

[0035] Step c: Synthesis of (E)-7-(3-benzylidene-2,5-dioxopyrrolidinyl)-N-hydroxyheptylamide (E)-7-(3-benzylidene-2,5-dioxopyrrolidinyl)heptanoate ethyl was used as a starting material, and the target compound was synthesized in the same manner as in step c of Example 1. A white solid was obtained (yield 16.1%). 1H NMR (400 MHz, DMSO-d6) δ 10.34 (s, 1H), 8.66 (s, 1H), 7.68 - 7.62 (m, 2H), 7.47 (qt, J = 6.9, 3.6 Hz, 4H), 3.71 (d, J = 2.4 Hz, 2H), 3.48 (t, J = 7.2 Hz, 2H), 1.94 (t, J = 7.4 Hz, 2H), 1.58 - 1.42 (m, 4H), 1.32 - 1.21 (m, 4H). 13C NMR (101 MHz, DMSO) δ 174.78, 171.15, 169.53, 134.60, 132.38, 130.70, 130.26, 129.44, 125.76, 38.48, 34.14, 32.64, 28.63, 27.67, 26.44, 25.45.

[0036] (Example 5) (E)-4-(3-benzylidene-2,5-dioxopyrrolidinyl)-N-hydroxyoctylamide(I-5)

[0037] [ka]

[0038] Step a: Synthesis of (E)-3-benzylidenepyrrolidine-2,5-dione The operation and input amounts are the same as in step a of Example 1.

[0039] Step b: Synthesis of ethyl (E)-8-(3-benzylidene-2,5-dioxopyrrolidinyl)heptanoate The target compound was synthesized using ethyl octanoate bromide as a raw material, by the same method as in step b of Example 1.

[0040] Step c: Synthesis of (E)-8-(3-benzylidene-2,5-dioxopyrrolidinyl)-N-hydroxyheptylamide (E)-8-(3-benzylidene-2,5-dioxopyrrolidinyl)heptanoate ethyl was used as a starting material, and the target compound was synthesized in the same manner as in step c of Example 1. A pale yellow solid was obtained (yield 20.2%). 1H NMR (400 MHz, DMSO-d6) δ 10.33 (s, 1H), 8.66 (s, 1H), 7.71 - 7.61 (m, 2H), 7.53 - 7.40 (m, 4H), 3.72 (d, J = 2.4 Hz, 2H), 3.48 (t, J = 7.2 Hz, 2H), 1.93 (t, J = 7.3 Hz, 2H), 1.56 - 1.43 (m, 4H), 1.31 - 1.19 (m, 6H). 13C NMR (101 MHz, DMSO) δ 174.76, 171.15, 169.60, 134.58, 132.40, 130.68, 130.25, 129.43, 125.72, 38.50, 34.13, 32.71, 28.94, 28.78, 27.75, 26.65, 25.53.

[0041] (Example 6) (E)-N-(2-amino-4-fluorophenyl)-4-(3-benzylidene-2,5-dioxopyrrolidinyl)butylamide(I-6)

[0042] [ka]

[0043] Step a: Synthesis of (E)-3-benzylidenepyrrolidine-2,5-dione The operation and input amounts are the same as in step a of Example 1.

[0044] Step b: Synthesis of ethyl (E)-4-(3-benzylidene-2,5-dioxopyrrolidinyl)butanoate The target compound was synthesized using ethyl bromide as a raw material, in the same manner as in step b of Example 1.

[0045] Step c: Synthesis of (E)-N-(2-amino-4-fluorophenyl)-4-(3-benzylidene-2,5-dioxopyrrolidinyl)butylamide (E)-4-(3-benzylidene-2,5-dioxopyrrolidinyl)butanoate ethyl and 4-fluoro-o-phenylenediamine were used as starting materials, and the target compound was synthesized in the same manner as in step c of Example 1. A white solid was obtained (yield 25.2%). 1H NMR (400 MHz, DMSO-d6) δ 9.01 (s, 1H), 7.69 - 7.62 (m, 2H), 7.52 - 7.42 (m, 4H), 7.11 - 7.01 (m, 1H), 6.48 (dd, J = 11.2, 2.9 Hz, 1H), 6.27 (td, J = 8.6, 2.9 Hz, 1H), 5.18 (s, 2H), 3.71 (d, J = 2.4 Hz, 2H), 3.57 (t, J = 6.9 Hz, 2H), 2.34 (t, J = 7.5 Hz, 2H), 1.88 (p, J = 7.1 Hz, 2H). 13C NMR (101 MHz, DMSO) δ 174.88, 171.25, 171.11, 162.25, 159.88, 145.06, 144.94, 134.58, 132.44, 130.70, 130.29, 129.47, 127.92, 127.82, 125.77, 119.76, 102.35, 102.13, 101.75, 101.50, 38.20, 34.22, 33.27, 23.78.

[0046] (Example 7) (E)-N-(2-amino-4-fluorophenyl)-5-(3-benzylidene-2,5-dioxopyrrolidinyl)pentylamide(I-7)

[0047] [ka]

[0048] Step a: Synthesis of (E)-3-benzylidenepyrrolidine-2,5-dione The operation and input amounts are the same as in step a of Example 1.

[0049] Step b: Synthesis of ethyl (E)-5-(3-benzylidene-2,5-dioxopyrrolidinyl)valerate The target compound was synthesized using ethyl bromide valerate as a raw material, in the same manner as in step b of Example 1.

[0050] Step c: Synthesis of (E)-N-(2-amino-4-fluorophenyl)-4-(3-benzylidene-2,5-dioxopyrrolidinyl)butylamide (E)-5-(3-benzylidene-2,5-dioxopyrrolidinyl) ethyl valerate and 4-fluoro-o-phenylenediamine were used as starting materials, and the target compound was synthesized in the same manner as in step c of Example 1. A white solid was obtained (yield 36.8%). 1H NMR (300 MHz, DMSO-d6) δ 9.03 (s, 1H), 7.72 - 7.59 (m, 2H), 7.55 - 7.37 (m, 4H), 7.09 (dd, J = 8.7, 6.3 Hz, 1H), 6.48 (dd, J = 11.2, 2.9 Hz, 1H), 6.30 (td, J = 8.5, 2.9 Hz, 1H), 5.15 (s, 2H), 3.73 (d, J = 2.3 Hz, 2H), 3.53 (t, J = 5.5 Hz, 2H), 2.33 (t, J = 6.9 Hz, 2H), 1.65 - 1.50 (m, 4H). 13C NMR (101 MHz, DMSO) δ 174.82, 171.53, 171.19, 162.13, 159.77, 144.78, 144.66, 134.59, 132.42, 130.70, 130.28, 129.45, 127.62, 127.52, 125.77, 119.95, 119.92, 102.43, 102.21, 101.89, 101.64, 38.37, 35.55, 34.17, 27.42, 22.97.

[0051] (Example 8) (E)-N-(2-amino-4-fluorophenyl)-6-(3-benzylidene-2,5-dioxopyrrolidinyl)hexylamide(I-8)

[0052] [ka]

[0053] Step a: Synthesis of (E)-3-benzylidenepyrrolidine-2,5-dione The operation and input amounts are the same as in step a of Example 1.

[0054] Step b: Synthesis of ethyl (E)-6-(3-benzylidene-2,5-dioxopyrrolidinyl)hexanoate The target compound was synthesized using ethyl bromide hexanoate as a raw material, in the same manner as in step b of Example 1.

[0055] Step c: Synthesis of (E)-N-(2-amino-4-fluorophenyl)-6-(3-benzylidene-2,5-dioxopyrrolidinyl)hexylamide (E)-6-(3-benzylidene-2,5-dioxopyrrolidinyl)hexanoate ethyl and 4-fluoro-o-phenylenediamine were used as starting materials, and the target compound was synthesized in the same manner as in step c of Example 1. A white solid was obtained (yield 36.8%). 1H NMR (300 MHz, DMSO-d6) δ 9.03 (s, 1H), 7.72 - 7.59 (m, 2H), 7.55 - 7.37 (m, 4H), 7.09 (dd, J = 8.7, 6.3 Hz, 1H), 6.48 (dd, J = 11.2, 2.9 Hz, 1H), 6.30 (td, J = 8.5, 2.9 Hz, 1H), 5.15 (s, 2H), 3.73 (d, J = 2.3 Hz, 2H), 3.53 (t, J = 5.5 Hz, 2H), 2.33 (t, J = 6.9 Hz, 2H), 1.65 - 1.50 (m, 4H). 13C NMR (101 MHz, DMSO) δ 174.82, 171.53, 171.19, 162.13, 159.77, 144.78, 144.66, 134.59, 132.42, 130.70, 130.28, 129.45, 127.62, 127.52, 125.77, 119.95, 119.92, 102.43, 102.21, 101.89, 101.64, 38.37, 35.55, 34.17, 27.42, 22.97.

[0056] (Example 9) (E)-N-(2-amino-4-fluorophenyl)-7-(3-benzylidene-2,5-dioxopyrrolidinyl)heptylamide(I-9)

[0057] [ka]

[0058] Step a: Synthesis of (E)-3-benzylidenepyrrolidine-2,5-dione The operation and input amounts are the same as in step a of Example 1.

[0059] Step b: Synthesis of ethyl (E)-7-(3-benzylidene-2,5-dioxopyrrolidinyl)heptanoate The target compound was synthesized using ethyl heptanoate bromide as a raw material, in the same manner as in step b of Example 1.

[0060] Step c: Synthesis of (E)-N-(2-amino-4-fluorophenyl)-7-(3-benzylidene-2,5-dioxopyrrolidinyl)heptylamide (E)-7-(3-benzylidene-2,5-dioxopyrrolidinyl)heptanoate ethyl and 4-fluoro-o-phenylenediamine were used as starting materials, and the target compound was synthesized in the same manner as in step c of Example 1. A white solid was obtained (yield 32.9%). 1H NMR (300 MHz, DMSO-d6) δ 9.02 (s, 1H), 7.73 - 7.59 (m, 2H), 7.53 - 7.37 (m, 4H), 7.09 (dd, J = 8.7, 6.3 Hz, 1H), 6.48 (dd, J = 11.2, 2.9 Hz, 1H), 6.29 (td, J = 8.6, 2.9 Hz, 1H), 5.13 (s, 2H), 3.72 (d, J = 2.4 Hz, 2H), 3.50 (t, J = 7.1 Hz, 2H), 2.29 (t, J = 7.4 Hz, 2H), 1.67 - 1.47 (m, 4H), 1.40 - 1.23 (m, 4H). 13C NMR (101 MHz, DMSO) δ 174.81, 171.82, 171.18, 162.39, 159.61, 144.77, 144.65, 134.60, 132.38, 130.70, 130.27, 129.45, 127.59, 127.49, 125.77, 120.04, 102.47, 102.24, 101.93, 101.68, 38.49, 36.03, 34.15, 28.75, 27.69, 26.52, 25.56.

[0061] (Example 10) 4-(3-((E)-benzylidene)-2,5-dioxopyrrolidinyl)-N-((1S,2S)-2-hydroxycyclohexyl)butylamide(I-10)

[0062] [ka]

[0063] Step a: Synthesis of (E)-3-benzylidenepyrrolidine-2,5-dione The operation and input amounts are the same as in step a of Example 1.

[0064] Step b: Synthesis of ethyl (E)-4-(3-benzylidene-2,5-dioxopyrrolidinyl)butanoate The target compound was synthesized using ethyl bromide as a raw material, in the same manner as in step b of Example 1.

[0065] Step c: Synthesis of 4-(3-((E)-benzylidene)-2,5-dioxopyrrolidinyl)-N-((1S,2S)-2-hydroxycyclohexyl)butylamide The target compound was synthesized using ethyl (E)-4-(3-benzylidene-2,5-dioxopyrrolidinyl)butanoate and (1S,2S)-2-aminocyclohexanol as starting materials, in the same manner as in step c of Example 1. A white solid was obtained (yield 35.8%). 1H NMR (400 MHz, DMSO-d6) δ 7.68 - 7.63 (m, 2H), 7.59 (d, J = 8.0 Hz, 1H), 7.52 - 7.42 (m, 4H), 4.50 (d, J = 4.8 Hz, 1H), 3.70 (d, J = 2.4 Hz, 2H), 3.51 (t, J = 7.1 Hz, 3H), 3.41 (m, 1H), 3.20 (m, 1H), 2.10 (t, J = 7.0 Hz, 2H), 1.76 (p, J = 7.5 Hz, 2H), 1.64 - 1.51 (m, 2H), 1.31 - 0.99 (m, 6H). 13C NMR (101 MHz, DMSO) δ 174.80, 171.57, 171.18, 134.60, 132.38, 130.69, 130.27, 129.47, 125.79, 71.73, 54.58, 38.32, 34.40, 34.20, 33.46, 31.42, 24.54, 24.19, 24.13.

[0066] (Example 11) 5-(3-((E)-benzylidene)-2,5-dioxopyrrolidinyl)-N-((1S,2S)-2-hydroxycyclohexyl)pentylamide(I-11)

[0067] [ka]

[0068] Step a: Synthesis of (E)-3-benzylidenepyrrolidine-2,5-dione The operation and input amounts are the same as in step a of Example 1.

[0069] Step b: Synthesis of ethyl (E)-5-(3-benzylidene-2,5-dioxopyrrolidinyl)valerate The target compound was synthesized using ethyl bromide valerate as a raw material, in the same manner as in step b of Example 1.

[0070] Step c: Synthesis of 5-(3-((E)-benzylidene)-2,5-dioxopyrrolidinyl)-N-((1S,2S)-2-hydroxycyclohexyl)pentylamide The target compound was synthesized using (E)-5-(3-benzylidene-2,5-dioxopyrrolidinyl) ethyl valerate and (1S,2S)-2-aminocyclohexanol as starting materials, in the same manner as in step c of Example 1. A white solid was obtained (yield 40.6%). 1H NMR (400 MHz, DMSO-d6) δ 7.69 - 7.63 (m, 2H), 7.57 (d, J = 7.8 Hz, 1H), 7.51 - 7.42 (m, 4H), 4.50 (d, J = 4.9 Hz, 1H), 3.72 (d, J = 2.5 Hz, 2H), 3.49 (t, J = 6.5 Hz, 2H), 3.42 - 3.36 (m, 1H), 3.20 (m, 1H), 2.09 (t, J = 6.6 Hz, 2H), 1.87 - 1.72 (m, 2H), 1.62 - 1.43 (m, 6H), 1.24 - 1.06 (m, 4H). 13C NMR (101 MHz, DMSO) δ 174.78, 172.09, 171.15, 134.59, 132.41, 130.70, 130.27, 129.45, 125.76, 71.74, 54.54, 38.39, 35.50, 34.47, 34.15, 31.46, 27.43, 24.53, 24.20, 23.16.

[0071] (Example 12) 6-(3-((E)-benzylidene)-2,5-dioxopyrrolidinyl)-N-((1S,2S)-2-hydroxycyclohexyl)hexylamide(I-12)

[0072] [ka]

[0073] Step a: Synthesis of (E)-3-benzylidenepyrrolidine-2,5-dione The operation and input amounts are the same as in step a of Example 1.

[0074] Step b: Synthesis of ethyl (E)-6-(3-benzylidene-2,5-dioxopyrrolidinyl)hexanoate The target compound was synthesized using ethyl bromide hexanoate as a raw material, in the same manner as in step b of Example 1.

[0075] Step c: Synthesis of 6-(3-((E)-benzylidene)-2,5-dioxopyrrolidinyl)-N-((1S,2S)-2-hydroxycyclohexyl)hexylamide The target compound was synthesized using ethyl (E)-6-(3-benzylidene-2,5-dioxopyrrolidinyl)hexanoate and (1S,2S)-2-aminocyclohexanol as starting materials, in the same manner as in step c of Example 1. A white solid was obtained (yield 38.5%). 1H NMR (400 MHz, DMSO-d6) δ 7.71 - 7.61 (m, 2H), 7.54 (d, J = 7.8 Hz, 1H), 7.52 - 7.41 (m, 4H), 4.48 (d, J = 5.1 Hz, 1H), 3.71 (d, J = 2.4 Hz, 2H), 3.48 (t, J = 7.1 Hz, 2H), 3.42 - 3.35 (m, 1H), 3.24 - 3.15 (m, 1H), 2.06 (t, J = 7.4 Hz, 2H), 1.86 - 1.70 (m, 2H), 1.64 - 1.45 (m, 6H), 1.30 - 1.00 (m, 6H). 13C NMR (101 MHz, DMSO) δ 174.75, 172.34, 171.13, 134.59, 132.39, 130.69, 130.26, 129.44, 125.74, 71.81, 54.55, 38.47, 35.81, 34.51, 34.14, 31.46, 27.61, 26.35, 25.41, 24.54, 24.21.

[0076] (Example 13) 7-(3-((E)-benzylidene)-2,5-dioxopyrrolidinyl)-N-((1S,2S)-2-hydroxycyclohexyl)heptylamide(I-13)

[0077] [ka]

[0078] Step a: Synthesis of (E)-3-benzylidenepyrrolidine-2,5-dione The operation and input amounts are the same as in step a of Example 1.

[0079] Step b: Synthesis of ethyl (E)-7-(3-benzylidene-2,5-dioxopyrrolidinyl)heptanoate The target compound was synthesized using ethyl heptanoate bromide as a raw material, in the same manner as in step b of Example 1.

[0080] Step c: Synthesis of 7-(3-((E)-benzylidene)-2,5-dioxopyrrolidinyl)-N-((1S,2S)-2-hydroxycyclohexyl)heptylamide The target compound was synthesized using ethyl (E)-7-(3-benzylidene-2,5-dioxopyrrolidinyl)heptanoate and (1S,2S)-2-aminocyclohexanol as starting materials, in the same manner as in step c of Example 1. A white solid was obtained (yield 48.1%). 1H NMR (400 MHz, DMSO-d6) δ 7.69 - 7.62 (m, 2H), 7.54 (d, J = 7.8 Hz, 1H), 7.51 - 7.42 (m, 4H), 4.48 (d, J = 5.0 Hz, 1H), 3.72 (d, J = 2.4 Hz, 2H), 3.48 (t, J = 7.2 Hz, 2H), 3.42 - 3.35 (m, 1H), 3.25 - 3.15 (m, 1H), 2.05 (t, J = 7.4 Hz, 2H), 1.87 - 1.70 (m, 2H), 1.64 - 1.40 (m, 6H), 1.29 - 1.22 (m, 4H), 1.22 - 1.07 (m, 4H). 13C NMR (101 MHz, DMSO) δ 174.79, 172.43, 171.16, 134.60, 132.37, 130.70, 130.26, 129.45, 125.78, 71.78, 54.53, 38.51, 35.94, 34.52, 34.14, 31.47, 28.70, 27.70, 26.53, 25.68, 24.54, 24.20.

[0081] (Example 14) 8-(3-((E)-benzylidene)-2,5-dioxopyrrolidinyl)-N-((1S,2S)-2-hydroxycyclohexyl)octylamide(I-14)

[0082] [ka]

[0083] Step a: Synthesis of (E)-3-benzylidenepyrrolidine-2,5-dione The operation and input amounts are the same as in step a of Example 1.

[0084] Step b: Synthesis of ethyl (E)-8-(3-benzylidene-2,5-dioxopyrrolidinyl)octanoate The target compound was synthesized using ethyl octanoate bromide as a raw material, by the same method as in step b of Example 1.

[0085] Step c: Synthesis of 8-(3-((E)-benzylidene)-2,5-dioxopyrrolidinyl)-N-((1S,2S)-2-hydroxycyclohexyl)octylamide The target compound was synthesized using ethyl (E)-8-(3-benzylidene-2,5-dioxopyrrolidinyl)octanoate and (1S,2S)-2-aminocyclohexanol as starting materials, in the same manner as in step c of Example 1. A white solid was obtained (yield 36.2%). 1H NMR (400 MHz, DMSO-d6) δ 7.69 - 7.61 (m, 2H), 7.54 (d, J = 7.8 Hz, 1H), 7.51 - 7.43 (m, 4H), 4.49 (d, J = 5.0 Hz, 1H), 3.72 (d, J = 2.4 Hz, 2H), 3.48 (t, J = 7.2 Hz, 2H), 3.42 - 3.35 (m, 1H), 3.24 - 3.15 (m, 1H), 2.05 (t, J = 7.4 Hz, 2H), 1.87 - 1.71 (m, 2H), 1.61 - 1.42 (m, 6H), 1.31 - 1.09 (m, 10H). 13C NMR (101 MHz, DMSO) δ 174.77, 172.49, 171.15, 134.61, 132.38, 130.69, 130.25, 129.44, 125.77, 71.79, 54.54, 38.51, 36.02, 34.50, 34.14, 31.46, 28.97, 28.84, 27.75, 26.66, 25.75, 24.54, 24.20.

[0086] (Example 15) (E)-7-(3-(4-isopropylbenzylidene)-2,5-dioxopyrrolidinyl)-N-hydroxyheptylamide(I-15)

[0087] [ka]

[0088] Step a: Synthesis of (E)-3-(4-isopropylbenzylidene)pyrrolidine-2,5-dione The target compound was synthesized using 4-isopropylbenzaldehyde as a raw material, in the same manner as in step a of Example 1.

[0089] Step b: Synthesis of ethyl (E)-7-(3-(4-isopropylbenzylidene)-2,5-dioxopyrrolidinyl)heptanoate The target compound was synthesized using ethyl heptanoate bromide as a raw material, in the same manner as in step b of Example 1.

[0090] Step c: Synthesis of (E)-7-(3-(4-isopropylbenzylidene)-2,5-dioxopyrrolidinyl)-N-hydroxyheptylamide (E)-7-(3-(4-isopropylbenzylidene)-2,5-dioxopyrrolidinyl)heptanoate ethyl was used as a starting material, and the target compound was synthesized in the same manner as in step c of Example 1. A white solid was obtained (yield 26.6%). 1H NMR (400 MHz, DMSO-d6) δ 10.33 (s, 1H), 8.65 (s, 1H), 7.57 (d, J = 8.1 Hz, 2H), 7.44 (t, J = 2.2 Hz, 1H), 7.36 (d, J = 8.2 Hz, 2H), 3.70 (d, J = 2.4 Hz, 2H), 3.47 (t, J = 7.2 Hz, 2H), 2.94 (hept, J = 6.8 Hz, 1H), 1.93 (t, J = 7.3 Hz, 2H), 1.56 - 1.42 (m, 4H), 1.28 - 1.20 (m, 10H). 13C NMR (101 MHz, DMSO) δ 174.84, 171.25, 169.51, 150.98, 132.40, 132.29, 130.87, 127.44, 124.69, 38.46, 34.14, 33.82, 32.64, 28.63, 27.68, 26.45, 25.45, 24.08.

[0091] (Example 16) (E)-7-(3-(4-dimethylaminobenzylidene)-2,5-dioxopyrrolidinyl)-N-hydroxyheptylamide(I-16)

[0092] [ka]

[0093] Step a: Synthesis of (E)-3-(4-dimethylaminobenzylidene)pyrrolidine-2,5-dione The target compound was synthesized using 4-dimethylaminobenzaldehyde as a raw material, by the same method as in step a of Example 1.

[0094] Step b: Synthesis of ethyl (E)-7-(3-(4-dimethylaminobenzylidene)-2,5-dioxopyrrolidinyl)heptanoate The target compound was synthesized using ethyl heptanoate bromide as a raw material, in the same manner as in step b of Example 1.

[0095] Step c: Synthesis of (E)-7-(3-(4-dimethylaminobenzylidene)-2,5-dioxopyrrolidinyl)-N-hydroxyheptylamide (E)-7-(3-(4-dimethylaminobenzylidene)-2,5-dioxopyrrolidinyl)heptanoate ethyl was used as a starting material, and the target compound was synthesized in the same manner as in step c of Example 1. A yellow solid was obtained (yield 32.1%). 1H NMR (300 MHz, DMSO-d6) δ 10.35 (s, 1H), 8.68 (s, 1H), 7.46 (d, J = 8.5 Hz, 2H), 7.35 (t, J = 2.0 Hz, 1H), 6.76 (d, J = 8.4 Hz, 2H), 3.61 (d, J = 2.2 Hz, 2H), 3.45 (t, J = 7.1 Hz, 2H), 2.99 (s, 6H), 1.93 (t, J = 7.3 Hz, 2H), 1.57 - 1.41 (m, 4H), 1.30 - 1.15 (m, 4H). 13C NMR (101 MHz, DMSO) δ 174.98, 171.51, 169.53, 151.56, 133.35, 132.48, 121.95, 119.01, 112.34, 40.10, 38.29, 34.25, 32.65, 28.64, 27.77, 26.46, 25.46.

[0096] (Example 17) (E)-7-(3-(4-trifluoromethylbenzylidene)-2,5-dioxopyrrolidinyl)-N-hydroxyheptylamide(I-17)

[0097] [ka]

[0098] Step a: Synthesis of (E)-3-(4-trifluoromethylbenzylidene)pyrrolidine-2,5-dione The target compound was synthesized using 4-trifluoromethylbenzaldehyde as a raw material, by the same method as in step a of Example 1.

[0099] Step b: Synthesis of ethyl (E)-7-(3-(4-trifluoromethylbenzylidene)-2,5-dioxopyrrolidinyl)heptanoate The target compound was synthesized using ethyl heptanoate bromide as a raw material, in the same manner as in step b of Example 1.

[0100] Step c: Synthesis of (E)-7-(3-(4-trifluoromethylbenzylidene)-2,5-dioxopyrrolidinyl)-N-hydroxyheptylamide (E)-7-(3-(4-trifluoromethylbenzylidene)-2,5-dioxopyrrolidinyl)heptanoate ethyl was used as a starting material, and the target compound was synthesized in the same manner as in step c of Example 1. A white solid was obtained (yield 15.8%). 1H NMR (400 MHz, DMSO-d6) δ 10.33 (s, 1H), 8.65 (s, 1H), 7.88 (d, J = 8.3 Hz, 2H), 7.82 (d, J = 8.3 Hz, 2H), 7.55 (t, J = 2.3 Hz, 1H), 3.77 (d, J = 2.4 Hz, 2H), 3.49 (t, J = 7.2 Hz, 2H), 1.93 (t, J = 7.4 Hz, 2H), 1.59 - 1.43 (m, 4H), 1.29 - 1.22 (m, 4H). 13C NMR (101 MHz, DMSO) δ 174.60, 170.84, 169.51, 138.61, 131.19, 130.53, 129.91, 129.59, 128.77, 126.16, 126.12, 125.83, 123.12, 38.58, 34.13, 32.63, 28.62, 27.62, 26.43, 25.44.

[0101] (Example 18) (E)-7-(3-(4-methylbenzylidene)-2,5-dioxopyrrolidinyl)-N-hydroxyheptylamide(I-18)

[0102] [ka]

[0103] Step a: Synthesis of (E)-3-(4-methylbenzylidene)pyrrolidine-2,5-dione The target compound was synthesized using 4-methylbenzaldehyde as a raw material, in the same manner as in step a of Example 1.

[0104] Step b: Synthesis of ethyl (E)-7-(3-(4-methylbenzylidene)-2,5-dioxopyrrolidinyl)heptanoate The target compound was synthesized using ethyl heptanoate bromide as a raw material, in the same manner as in step b of Example 1.

[0105] Step c: Synthesis of (E)-7-(3-(4-methylbenzylidene)-2,5-dioxopyrrolidinyl)-N-hydroxyheptylamide (E)-7-(3-(4-methylbenzylidene)-2,5-dioxopyrrolidinyl)heptanoate ethyl was used as a starting material, and the target compound was synthesized in the same manner as in step c of Example 1. A white solid was obtained (yield 26.7%). 1H NMR (400 MHz, DMSO-d6) δ 10.33 (s, 1H), 8.65 (s, 1H), 7.54 (d, J = 5.8 Hz, 2H), 7.47 - 7.40 (m, 1H), 7.30 (d, J = 5.8 Hz, 2H), 3.69 (d, J = 2.9 Hz, 2H), 3.48 (t, J = 6.0 Hz, 2H), 2.36 (s, 3H), 1.94 (t, J = 6.9 Hz, 2H), 1.56 - 1.41 (m, 4H), 1.30 - 1.19 (m, 4H). 13C NMR (101 MHz, DMSO) δ 174.82, 171.24, 169.52, 140.28, 132.42, 131.88, 130.73, 130.08, 124.62, 38.44, 34.16, 32.64, 28.62, 27.68, 26.43, 25.44, 21.48.

[0106] (Example 19) (E)-7-(3-(2-methylbenzylidene)-2,5-dioxopyrrolidinyl)-N-hydroxyheptylamide(I-19)

[0107] [ka]

[0108] Step a: Synthesis of (E)-3-(2-methylbenzylidene)pyrrolidine-2,5-dione The target compound was synthesized using 2-methylbenzaldehyde as a raw material, by the same method as in step a of Example 1.

[0109] Step b: Synthesis of ethyl (E)-7-(3-(2-methylbenzylidene)-2,5-dioxopyrrolidinyl)heptanoate The target compound was synthesized using ethyl heptanoate bromide as a raw material, in the same manner as in step b of Example 1.

[0110] Step c: Synthesis of (E)-7-(3-(2-methylbenzylidene)-2,5-dioxopyrrolidinyl)-N-hydroxyheptylamide (E)-7-(3-(2-methylbenzylidene)-2,5-dioxopyrrolidinyl)heptanoate ethyl was used as a starting material, and the target compound was synthesized in the same manner as in step c of Example 1. A white solid was obtained (yield 35.2%). 1H NMR (400 MHz, DMSO-d6) δ 10.35 (s, 1H), 8.68 (s, 1H), 7.64 (t, J = 2.4 Hz, 1H), 7.56 (d, J = 7.1 Hz, 1H), 7.36 - 7.25 (m, 3H), 3.65 (d, J = 2.4 Hz, 2H), 3.48 (t, J = 7.2 Hz, 2H), 2.39 (s, 3H), 1.93 (t, J = 7.4 Hz, 2H), 1.58 - 1.44 (m, 4H), 1.29 - 1.20 (m, 4H). 13C NMR (101 MHz, DMSO) δ 174.88, 171.07, 169.57, 138.63, 133.24, 131.10, 130.06, 129.81, 128.65, 126.81, 126.45, 38.47, 33.77, 32.64, 28.61, 27.66, 26.44, 25.43, 19.94.

[0111] (Example 20) (E)-7-(3-(2-cyanobenzylidene)-2,5-dioxopyrrolidinyl)-N-hydroxyheptylamide(I-20)

[0112] [ka]

[0113] Step a: Synthesis of (E)-3-(2-cyanobenzylidene)pyrrolidine-2,5-dione The target compound was synthesized using 2-cyanobenzaldehyde as a raw material, in the same manner as in step a of Example 1.

[0114] Step b: Synthesis of ethyl (E)-7-(3-(2-cyanobenzylidene)-2,5-dioxopyrrolidinyl)heptanoate The target compound was synthesized using ethyl heptanoate bromide as a raw material, in the same manner as in step b of Example 1.

[0115] Step c: Synthesis of (E)-7-(3-(2-cyanobenzylidene)-2,5-dioxopyrrolidinyl)-N-hydroxyheptylamide (E)-7-(3-(2-cyanobenzylidene)-2,5-dioxopyrrolidinyl)heptanoate ethyl was used as a starting material, and the target compound was synthesized in the same manner as in step c of Example 1. A white solid was obtained (yield 12.1%). 1H NMR (400 MHz, DMSO-d6) δ 10.33 (s, 1H), 8.65 (s, 1H), 7.99 (dd, J = 7.8, 1.4 Hz, 1H), 7.90 (d, J = 7.9 Hz, 1H), 7.82 (td, J = 7.8, 1.4 Hz, 1H), 7.67 - 7.61 (m, 2H), 3.77 (d, J = 2.5 Hz, 2H), 3.50 (t, J = 7.1 Hz, 2H), 1.94 (t, J = 7.4 Hz, 2H), 1.60 - 1.44 (m, 4H), 1.30 - 1.22 (m, 4H). 13C NMR (101 MHz, DMSO) δ 174.43, 170.56, 169.53, 136.91, 134.17, 134.16, 130.86, 130.59, 129.42, 126.63, 117.72, 113.25, 38.70, 34.04, 32.65, 28.62, 27.59, 26.44, 25.44.

[0116] (Example 21) (E)-7-(3-(2-pyridylmethylidene)-2,5-dioxopyrrolidinyl)-N-hydroxyheptylamide(I-21)

[0117] [ka]

[0118] Step a: Synthesis of (E)-3-(2-pyridylmethylidene)pyrrolidine-2,5-dione The target compound was synthesized using 2-pyridinecarboxaldehyde as a raw material, by the same method as in step a of Example 1.

[0119] Step b: Synthesis of ethyl (E)-7-(3-(2-pyridylmethylidene)-2,5-dioxopyrrolidinyl)heptanoate The target compound was synthesized using ethyl heptanoate bromide as a raw material, in the same manner as in step b of Example 1.

[0120] Step c: Synthesis of (E)-7-(3-(2-pyridylmethylidene)-2,5-dioxopyrrolidinyl)-N-hydroxyheptylamide (E)-7-(3-(2-pyridylmethylidene)-2,5-dioxopyrrolidinyl)heptanoate ethyl was used as a starting material, and the target compound was synthesized in the same manner as in step c of Example 1. A yellow solid was obtained (yield 16.8%). 1H NMR (300 MHz, DMSO-d6) δ 10.35 (s, 1H), 8.73 (d, J = 4.5 Hz, 1H), 8.68 (s, 1H), 7.90 (td, J = 7.7, 1.8 Hz, 1H), 7.76 (d, J = 7.7 Hz, 1H), 7.48 (t, J = 2.2 Hz, 1H), 7.40 (ddd, J = 7.5, 4.7, 1.3 Hz, 1H), 3.78 (d, J = 2.3 Hz, 2H), 3.48 (t, J = 7.2 Hz, 2H), 1.93 (t, J = 7.3 Hz, 2H), 1.59 - 1.42 (m, 4H), 1.32 - 1.19 (m, 4H). 13C NMR (101 MHz, DMSO) δ 175.36, 171.10, 169.66, 153.68, 150.53, 137.58, 130.42, 129.55, 127.54, 124.19, 38.45, 35.37, 32.61, 28.58, 27.62, 26.40, 25.41.

[0121] (Example 22) (E)-7-(3-(2-naphthylmethylidene)-2,5-dioxopyrrolidinyl)-N-hydroxyheptylamide(I-22)

[0122] [ka]

[0123] Step a: Synthesis of (E)-3-(2-naphthylmethylidene)pyrrolidine-2,5-dione The target compound was synthesized using 2-naphthalenecarboxaldehyde as a raw material, by the same method as in step a of Example 1.

[0124] Step b: Synthesis of ethyl (E)-7-(3-(2-naphthylmethylidene)-2,5-dioxopyrrolidinyl)heptanoate The target compound was synthesized using ethyl heptanoate bromide as a raw material, in the same manner as in step b of Example 1.

[0125] Step c: Synthesis of (E)-7-(3-(2-naphthylmethylidene)-2,5-dioxopyrrolidinyl)-N-hydroxyheptylamide (E)-7-(3-(2-naphthylmethylidene)-2,5-dioxopyrrolidinyl)heptanoate ethyl was used as a starting material, and the target compound was synthesized in the same manner as in step c of Example 1. A white solid was obtained (yield 18.2%). 1H NMR (400 MHz, DMSO-d6) δ 10.33 (s, 1H), 8.66 (s, 1H), 8.25 (s, 1H), 8.07 - 7.92 (m, 3H), 7.77 (dd, J = 8.6, 1.8 Hz, 1H), 7.63 (t, J = 2.4 Hz, 1H), 7.61 - 7.55 (m, 2H), 3.85 (d, J = 2.3 Hz, 2H), 3.50 (t, J = 7.2 Hz, 2H), 1.94 (t, J = 7.4 Hz, 2H), 1.50 (m, 4H), 1.27 (m, 4H). 13C NMR (101 MHz, DMSO) δ 174.88, 171.20, 169.56, 133.59, 133.33, 132.41, 132.20, 131.18, 129.11, 128.94, 128.05, 127.97, 127.23, 127.18, 126.05, 38.52, 34.29, 32.64, 28.62, 27.67, 26.45, 25.45.

[0126] (Example 23) (E)-7-(3-(2-thienylmethylidene)-2,5-dioxopyrrolidinyl)-N-hydroxyheptylamide(I-23)

[0127] [ka]

[0128] Step a: Synthesis of (E)-3-(2-thienylmethylidene)pyrrolidine-2,5-dione The target compound was synthesized using 2-thiophenecarboxaldehyde as a starting material, by the same method as in step a of Example 1.

[0129] Step b: Synthesis of ethyl (E)-7-(3-(2-thienylmethylidene)-2,5-dioxopyrrolidinyl)heptanoate The target compound was synthesized using ethyl heptanoate bromide as a raw material, in the same manner as in step b of Example 1.

[0130] Step c: Synthesis of (E)-7-(3-(2-thienylmethylidene)-2,5-dioxopyrrolidinyl)-N-hydroxyheptylamide (E)-7-(3-(2-thienylmethylidene)-2,5-dioxopyrrolidinyl)heptanoate ethyl was used as a starting material, and the target compound was synthesized in the same manner as in step c of Example 1. A yellow solid was obtained (yield 18.6%). 1H NMR (400 MHz, DMSO-d6) δ 10.36 (s, 1H), 8.69 (s, 1H), 7.90 (d, J = 5.0 Hz, 1H), 7.72 (t, J = 2.4 Hz, 1H), 7.60 (d, J = 3.7 Hz, 1H), 7.24 (t, J = 4.3 Hz, 1H), 3.52 (d, J = 2.3 Hz, 2H), 3.46 (t, J = 7.2 Hz, 2H), 1.93 (t, J = 7.3 Hz, 2H), 1.58 - 1.42 (m, 4H), 1.29 - 1.18 (m, 4H). 13C NMR (101 MHz, DMSO) δ 174.23, 170.77, 169.55, 138.65, 133.73, 132.12, 128.88, 125.49, 122.97, 38.52, 34.12, 32.63, 28.62, 27.69, 26.42, 25.45.

[0131] (Example 24) (E)-7-(3-(2-chlorobenzylidene)-2,5-dioxopyrrolidinyl)-N-hydroxyheptylamide(I-24)

[0132] [ka]

[0133] Step a: Synthesis of (E)-3-(2-chlorobenzylidene)pyrrolidine-2,5-dione The target compound was synthesized using 2-chlorobenzaldehyde as a raw material, in the same manner as in step a of Example 1.

[0134] Step b: Synthesis of ethyl (E)-7-(3-(2-chlorobenzylidene)-2,5-dioxopyrrolidinyl)heptanoate The target compound was synthesized using ethyl heptanoate bromide as a raw material, in the same manner as in step b of Example 1.

[0135] Step c: Synthesis of (E)-7-(3-(2-chlorobenzylidene)-2,5-dioxopyrrolidinyl)-N-hydroxyheptylamide (E)-7-(3-(2-chlorobenzylidene)-2,5-dioxopyrrolidinyl)heptanoate ethyl was used as a starting material, and the target compound was synthesized in the same manner as in step c of Example 1. A pale yellow solid was obtained (yield 10.2%). 1H NMR (300 MHz, DMSO-d6) δ 10.34 (s, 1H), 8.67 (s, 1H), 7.80 - 7.73 (m, 1H), 7.71 (t, J = 2.2 Hz, 1H), 7.64 - 7.57 (m, 1H), 7.50 - 7.41 (m, 2H), 3.71 (d, J = 2.4 Hz, 2H), 3.49 (t, J = 7.1 Hz, 2H), 1.94 (t, J = 7.3 Hz, 2H), 1.60 - 1.40 (m, 4H), 1.31 - 1.18 (m, 4H). 13C NMR (101 MHz, DMSO) δ 174.63, 170.79, 169.55, 134.82, 132.19, 131.72, 130.45, 130.42, 128.77, 128.23, 127.33, 38.59, 33.68, 32.64, 28.61, 27.61, 26.43, 25.43.

[0136] (Example 25) (E)-7-(3-(3-chlorobenzylidene)-2,5-dioxopyrrolidinyl)-N-hydroxyheptylamide(I-25)

[0137] [ka]

[0138] Step a: Synthesis of (E)-3-(3-chlorobenzylidene)pyrrolin-2,5-dione The target compound was synthesized using 3-chlorobenzaldehyde as a raw material, by the same method as in step a of Example 1.

[0139] Step b: Synthesis of ethyl (E)-7-(3-(3-chlorobenzylidene)-2,5-dioxopyrrolidinyl)heptanoate The target compound was synthesized using ethyl heptanoate bromide as a raw material, in the same manner as in step b of Example 1.

[0140] Step c: Synthesis of (E)-7-(3-(3-chlorobenzylidene)-2,5-dioxopyrrolidinyl)-N-hydroxyheptylamide (E)-7-(3-(3-chlorobenzylidene)-2,5-dioxopyrrolidinyl)heptanoate ethyl was used as a starting material, and the target compound was synthesized in the same manner as in step c of Example 1. A pale yellow solid was obtained (yield 12.6%). 1H NMR (400 MHz, DMSO-d6) δ 10.33 (s, 1H), 8.65 (s, 1H), 7.72 (s, 1H), 7.65 - 7.60 (m, 1H), 7.50 (d, J = 4.5 Hz, 2H), 7.47 (t, J = 2.4 Hz, 1H), 3.75 (d, J = 2.4 Hz, 2H), 3.48 (t, J = 7.2 Hz, 2H), 1.93 (t, J = 7.3 Hz, 2H), 1.57 - 1.42 (m, 4H), 1.30 - 1.21 (m, 4H). 13C NMR (101 MHz, DMSO) δ 174.67, 170.93, 169.59, 136.74, 134.14, 131.23, 130.83, 130.18, 129.93, 128.97, 127.49, 38.54, 34.00, 32.62, 28.59, 27.61, 26.41, 25.43.

[0141] (Example 26) (E)-7-(3-(4-chlorobenzylidene)-2,5-dioxopyrrolidinyl)-N-hydroxyheptylamide(I-26)

[0142] [ka]

[0143] Step a: Synthesis of (E)-3-(4-chlorobenzylidene)pyrrolidine-2,5-dione The target compound was synthesized using 4-chlorobenzaldehyde as a raw material, in the same manner as in step a of Example 1.

[0144] Step b: Synthesis of ethyl (E)-7-(3-(4-chlorobenzylidene)-2,5-dioxopyrrolidinyl)heptanoate The target compound was synthesized using ethyl heptanoate as a raw material, in the same manner as in step b of Example 1.

[0145] Step c: Synthesis of (E)-7-(3-(4-chlorobenzylidene)-2,5-dioxopyrrolidinyl)-N-hydroxyheptylamide (E)-7-(3-(4-chlorobenzylidene)-2,5-dioxopyrrolidinyl)heptanoate ethyl was used as a starting material, and the target compound was synthesized in the same manner as in step c of Example 1. A yellow solid was obtained (yield 15.8%). 1H NMR (400 MHz, DMSO-d6) δ 10.33 (s, 1H), 8.65 (s, 1H), 7.68 (d, J = 8.7 Hz, 2H), 7.54 (d, J = 8.5 Hz, 2H), 7.47 (t, J = 2.4 Hz, 1H), 3.71 (d, J = 2.4 Hz, 2H), 3.48 (t, J = 7.2 Hz, 2H), 1.93 (t, J = 7.4 Hz, 2H), 1.59 - 1.42 (m, 4H), 1.33 - 1.20 (m, 4H). 13C NMR (101 MHz, DMSO) δ 174.67, 171.01, 169.55, 134.86, 133.53, 132.35, 131.01, 129.46, 126.59, 38.52, 34.07, 32.64, 28.61, 27.63, 26.42, 25.43.

[0146] (Example 27) (E)-7-(3-(3-bromobenzylidene)-2,5-dioxopyrrolidinyl)-N-hydroxyheptylamide(I-27)

[0147] [ka]

[0148] Step a: Synthesis of (E)-3-(3-bromobenzylidene)pyrrolidine-2,5-dione The target compound was synthesized using 3-bromobenzaldehyde as a raw material, in the same manner as in step a of Example 1.

[0149] Step b: Synthesis of ethyl (E)-7-(3-(3-bromobenzylidene)-2,5-dioxopyrrolidinyl)heptanoate The target compound was synthesized using ethyl heptanoate bromide as a raw material, in the same manner as in step b of Example 1.

[0150] Step c: Synthesis of (E)-7-(3-(3-bromobenzylidene)-2,5-dioxopyrrolidinyl)-N-hydroxyheptylamide (E)-7-(3-(3-bromobenzylidene)-2,5-dioxopyrrolidinyl)heptanoate ethyl was used as a starting material, and the target compound was synthesized in the same manner as in step c of Example 1. A white solid was obtained (yield 26.2%). 1H NMR (400 MHz, DMSO-d6) δ 10.35 (s, 1H), 8.68 (s, 1H), 7.85 (s, 1H), 7.70 - 7.60 (m, 2H), 7.46 (t, J = 2.3 Hz, 1H), 7.43 (d, J = 7.8 Hz, 1H), 3.75 (d, J = 2.4 Hz, 2H), 3.48 (t, J = 7.1 Hz, 2H), 1.93 (t, J = 7.3 Hz, 2H), 1.57 - 1.43 (m, 4H), 1.29 - 1.21 (m, 4H). 13C NMR (101 MHz, DMSO) δ 174.67, 170.90, 169.52, 137.03, 133.11, 132.82, 131.47, 130.75, 129.27, 127.49, 122.71, 38.53, 34.00, 32.63, 28.61, 27.64, 26.43, 25.44.

[0151] (Example 28) (E)-7-(3-(3-fluorobenzylidene)-2,5-dioxopyrrolidinyl)-N-hydroxyheptylamide(I-28)

[0152] [ka]

[0153] Step a: Synthesis of (E)-3-(3-fluorobenzylidene)pyrrolidine-2,5-dione The target compound was synthesized using 3-fluorobenzaldehyde as a raw material, in the same manner as in step a of Example 1.

[0154] Step b: Synthesis of ethyl (E)-7-(3-(3-fluorobenzylidene)-2,5-dioxopyrrolidinyl)heptanoate The target compound was synthesized using ethyl heptanoate bromide as a raw material, in the same manner as in step b of Example 1.

[0155] Step c: Synthesis of (E)-7-(3-(3-fluorobenzylidene)-2,5-dioxopyrrolidinyl)-N-hydroxyheptylamide (E)-7-(3-(3-fluorobenzylidene)-2,5-dioxopyrrolidinyl)heptanoate ethyl was used as a starting material, and the target compound was synthesized in the same manner as in step c of Example 1. A white solid was obtained (yield 29.6%). 1H NMR (400 MHz, DMSO-d6) δ 10.33 (s, 1H), 8.66 (s, 1H), 7.59 -7.44 (m, 4H), 7.34 - 7.22 (m, 1H), 3.75 (d, J = 2.4 Hz, 2H), 3.48 (t, J = 7.2 Hz, 2H), 1.93 (t, J = 7.4 Hz, 2H), 1.58 - 1.42 (m, 4H), 1.32 - 1.18 (m, 4H). 13C NMR (101 MHz, DMSO) δ 174.69, 170.96, 169.52, 163.94, 161.51, 136.99, 136.91, 131.42, 131.34, 131.03, 127.35, 126.85, 126.82, 117.13, 117.06, 116.92, 116.84, 38.53, 34.02, 32.63, 28.62, 27.64, 26.43, 25.44.

[0156] (Example 29) (E)-7-(3-(3-iodobenzylidene)-2,5-dioxopyrrolidinyl)-N-hydroxyheptylamide(I-29)

[0157] [ka]

[0158] Step a: Synthesis of (E)-3-(3-iodobenzylidene)pyrrolidine-2,5-dione The target compound was synthesized using 3-iodobenzaldehyde as a raw material, in the same manner as in step a of Example 1.

[0159] Process b: Synthesis of ethyl (E)-7-(3-(3-iodobenzylidene)-2,5-dioxopyrrolidinyl)heptanoate Using ethyl heptanoate bromide as a raw material, the target compound was synthesized in the same manner as in Process b of Example 1.

[0160] Process c: Synthesis of (E)-7-(3-(3-iodobenzylidene)-2,5-dioxopyrrolidinyl)-N-hydroxyheptylamide (E)-7-(3-(3-iodobenzylidene)-2,5-dioxopyrrolidinyl)ethyl heptanoate was used as a raw material, and the target compound was synthesized in the same manner as in Process c of Example 1. A white solid was obtained (yield 18.6%). 1H NMR (300 MHz, DMSO-d6) δ 10.35 (s, 1H), 8.69 (s, 1H), 8.00 (s, 1H), 7.80 (d, J = 7.6 Hz, 1H), 7.67 (d, J = 7.8 Hz, 1H), 7.41 (t, J = 2.4 Hz, 1H), 7.27 (t, J = 7.8 Hz, 1H), 3.73 (d, J = 2.4 Hz, 2H), 3.47 (t, J = 7.1 Hz, 2H), 1.93 (t, J = 7.3 Hz, 2H), 1.57 - 1.40 (m, 4H), 1.29 - 1.18 (m, 4H). 13C NMR (101 MHz, DMSO) δ 174.68, 170.91, 169.52, 138.95, 138.67, 136.92, 131.41, 130.79, 129.55, 127.19, 95.92, 38.52, 33.98, 32.62, 28.61, 27.64, 26.42, 25.44.

[0161] (Example 30) (E)-7-(3-(3,4-dichlorobenzylidene)-2,5-dioxopyrrolidinyl)-N-hydroxyheptylamide (I-30)

[0162]

Chemical Structure

[0163] Step a: Synthesis of (E)-3-(3,4-dichlorobenzylidene)pyrrolin-2,5-dione The target compound was synthesized using 3,4-dichlorobenzaldehyde as a raw material, by the same method as in step a of Example 1.

[0164] Step b: Synthesis of ethyl (E)-7-(3-(3,4-dichlorobenzylidene)-2,5-dioxopyrrolidinyl)heptanoate The target compound was synthesized using ethyl heptanoate bromide as a raw material, in the same manner as in step b of Example 1.

[0165] Step c: Synthesis of (E)-7-(3-(3,4-dichlorobenzylidene)-2,5-dioxopyrrolidinyl)-N-hydroxyheptylamide (E)-7-(3-(3,4-dichlorobenzylidene)-2,5-dioxopyrrolidinyl)heptanoate ethyl was used as a starting material, and the target compound was synthesized in the same manner as in step c of Example 1. A yellow solid was obtained (yield 18.5%). 1H NMR (400 MHz, DMSO-d6) δ 10.33 (s, 1H), 8.65 (s, 1H), 7.92 (s, 1H), 7.72 (d, J = 8.3 Hz, 1H), 7.64 (d, J = 8.4 Hz, 1H), 7.46 (s, 1H), 3.75 (s, 2H), 3.48 (t, J = 7.1 Hz, 2H), 1.93 (t, J = 7.3 Hz, 2H), 1.57 - 1.41 (m, 4H), 1.30 - 1.17 (m, 4H). 13C NMR (101 MHz, DMSO) δ 174.56, 170.78, 169.51, 135.38, 132.63, 132.33, 132.19, 131.48, 130.26, 129.78, 128.08, 38.57, 33.94, 32.64, 28.62, 27.62, 26.43, 25.44.

[0166] (Example 31) (E)-7-(3-(2-methoxybenzylidene)-2,5-dioxopyrrolidinyl)-N-hydroxyheptylamide(I-31)

[0167] [ka]

[0168] Step a: Synthesis of (E)-3-(2-methoxybenzylidene)pyrrolidine-2,5-dione The target compound was synthesized using 2-methoxybenzaldehyde as a raw material, in the same manner as in step a of Example 1.

[0169] Step b: Synthesis of ethyl (E)-7-(3-(2-methoxybenzylidene)-2,5-dioxopyrrolidinyl)heptanoate The target compound was synthesized using ethyl heptanoate bromide as a raw material, in the same manner as in step b of Example 1.

[0170] Step c: Synthesis of (E)-7-(3-(2-methoxybenzylidene)-2,5-dioxopyrrolidinyl)-N-hydroxyheptylamide (E)-7-(3-(2-methoxybenzylidene)-2,5-dioxopyrrolidinyl)heptanoate ethyl was used as a starting material, and the target compound was synthesized in the same manner as in step c of Example 1. A white solid was obtained (yield 19.3%). 1H NMR (400 MHz, DMSO-d6) δ 10.33 (s, 1H), 8.65 (s, 1H), 7.77 (t, J = 2.4 Hz, 1H), 7.57 (dd, J = 7.8, 1.6 Hz, 1H), 7.44 (ddd, J = 8.7, 7.3, 1.7 Hz, 1H), 7.12 (dd, J = 8.4, 1.1 Hz, 1H), 7.07 - 7.01 (m, 1H), 3.88 (s, 3H), 3.66 (d, J = 2.4 Hz, 2H), 3.47 (t, J = 7.1 Hz, 2H), 1.93 (t, J = 7.4 Hz, 2H), 1.56 - 1.42 (m, 4H), 1.29 - 1.20 (m, 4H). 13C NMR (101 MHz, DMSO) δ 174.92, 171.26, 169.57, 158.48, 132.06, 129.58, 126.54, 125.25, 122.92, 121.16, 111.99, 56.18, 38.43, 33.95, 32.63, 28.61, 27.67, 26.43, 25.44.

[0171] (Example 32) (E)-7-(3-(3-Methoxybenzylidene)-2,5-dioxopyrrolidinyl)-N-hydroxyheptanamide (I-32)

[0172] [Chemical Structure]

[0173] Step a: Synthesis of (E)-3-(Methoxybenzylidene)pyrrolidine-2,5-dione Using 3-methoxybenzaldehyde as the raw material, the target compound was synthesized in the same manner as in Step a of Example 1.

[0174] Step b: Synthesis of Ethyl (E)-7-(3-(3-Methoxybenzylidene)-2,5-dioxopyrrolidinyl)heptanoate The target compound was synthesized using ethyl heptanoate bromide as a raw material, in the same manner as in step b of Example 1.

[0175] Step c: Synthesis of (E)-7-(3-(3-methoxybenzylidene)-2,5-dioxopyrrolidinyl)-N-hydroxyheptylamide (E)-7-(3-(3-methoxybenzylidene)-2,5-dioxopyrrolidinyl)heptanoate ethyl was used as a starting material, and the target compound was synthesized in the same manner as in step c of Example 1. A white solid was obtained (yield 10.3%). 1H NMR (400 MHz, DMSO-d6) δ 10.35 (s, 1H), 8.68 (s, 1H), 7.45 (s, 1H), 7.39 (t, J = 8.0 Hz, 1H), 7.22 (d, J = 7.8 Hz, 1H), 7.19 (s, 1H), 7.02 (d, J = 8.2 Hz, 1H), 3.81 (s, 3H), 3.74 (s, 2H), 3.48 (t, J = 7.2 Hz, 2H), 1.93 (t, J = 7.4 Hz, 2H), 1.61 - 1.41 (m, 4H), 1.32 - 1.20 (m, 4H). 13C NMR (101 MHz, DMSO) δ 174.77, 171.12, 169.52, 159.94, 135.93, 132.39, 130.49, 126.01, 122.96, 116.23, 115.69, 55.67, 38.48, 34.08, 32.64, 28.62, 27.66, 26.43, 25.45.

[0176] (Example 33) (E)-7-(3-(4-methoxybenzylidene)-2,5-dioxopyrrolidinyl)-N-hydroxyheptylamide(I-33)

[0177] [ka]

[0178] Step a: Synthesis of (E)-3-(4-methoxybenzylidene)pyrrolidine-2,5-dione The target compound was synthesized using 4-methoxybenzaldehyde as a raw material, by the same method as in step a of Example 1.

[0179] Step b: Synthesis of ethyl (E)-7-(3-(4-methoxybenzylidene)-2,5-dioxopyrrolidinyl)heptanoate The target compound was synthesized using ethyl heptanoate bromide as a raw material, in the same manner as in step b of Example 1.

[0180] Step c: Synthesis of (E)-7-(3-(4-methoxybenzylidene)-2,5-dioxopyrrolidinyl)-N-hydroxyheptylamide (E)-7-(3-(4-methoxybenzylidene)-2,5-dioxopyrrolidinyl)heptanoate ethyl was used as a starting material, and the target compound was synthesized in the same manner as in step c of Example 1. A white solid was obtained (yield 12.5%). 1H NMR (400 MHz, DMSO-d6) δ 10.34 (s, 1H), 8.67 (s, 1H), 7.61 (d, J = 9.1 Hz, 2H), 7.43 (t, J = 2.4 Hz, 1H), 7.04 (d, J = 7.9 Hz, 2H), 3.82 (s, 3H), 3.66 (d, J = 2.1 Hz, 2H), 3.46 (t, J = 7.2 Hz, 2H), 1.93 (t, J = 7.3 Hz, 2H), 1.53 - 1.43 (m, 4H), 1.26 - 1.22 (m, 4H). 13C NMR (101 MHz, DMSO) δ 174.89, 171.35, 169.58, 160.98, 132.60, 132.32, 127.21, 122.77, 114.97, 55.82, 38.40, 34.08, 32.63, 28.61, 27.69, 26.43, 25.44.

[0181] (Example 34) (E)-7-(3-(3,4-dimethoxybenzylidene)-2,5-dioxopyrrolidinyl)-N-hydroxyheptylamide(I-34)

[0182] [ka]

[0183] Step a: Synthesis of (E)-3-(3,4-dimethoxybenzylidene)pyrrolidine-2,5-dione The target compound was synthesized using 3,4-dimethoxybenzaldehyde as a raw material, by the same method as in step a of Example 1.

[0184] Step b: Synthesis of (E)-7-(3-(3,4-dimethoxybenzylidene)-2,5-dioxopyrrolidinyl)heptanoate ethyl The target compound was synthesized using ethyl heptanoate bromide as a raw material, in the same manner as in step b of Example 1.

[0185] Step c: Synthesis of (E)-7-(3-(3,4-dimethoxybenzylidene)-2,5-dioxopyrrolidinyl)-N-hydroxyheptylamide (E)-7-(3-(3,4-dimethoxybenzylidene)-2,5-dioxopyrrolidinyl)heptanoate ethyl was used as a starting material, and the target compound was synthesized in the same manner as in step c of Example 1. A white solid was obtained (yield 21.5%). 1H NMR (400 MHz, DMSO-d6) δ 10.33 (s, 1H), 8.65 (s, 1H), 7.43 (t, J = 2.3 Hz, 1H), 7.23 (dd, J = 8.4, 2.1 Hz, 1H), 7.20 (d, J = 2.0 Hz, 1H), 7.05 (d, J = 8.4 Hz, 1H), 3.83 (s, 3H), 3.82 (s, 3H), 3.73 (d, J = 2.3 Hz, 2H), 3.47 (t, J = 7.1 Hz, 2H), 1.93 (t, J = 7.3 Hz, 2H), 1.54 - 1.43 (m, 4H), 1.28 - 1.22 (m, 4H). 13C NMR (101 MHz, DMSO) δ 174.92, 171.32, 169.52, 150.82, 149.22, 132.76, 127.38, 124.63, 122.83, 113.58, 112.26, 56.06, 55.99, 38.41, 33.98, 32.64, 28.63, 27.70, 26.44, 25.46.

[0186] (Example 35) (E)-7-(3-(3,4,5-trimethoxybenzylidene)-2,5-dioxopyrrolidinyl)-N-hydroxyheptylamide(I-35)

[0187] [ka]

[0188] Step a: Synthesis of (E)-3-(3,4,5-trimethoxybenzylidene)pyrrolidine-2,5-dione The target compound was synthesized using 3,4,5-trimethoxybenzaldehyde as a starting material, by the same method as in step a of Example 1.

[0189] Step b: Synthesis of ethyl (E)-7-(3-(3,4,5-trimethoxybenzylidene)-2,5-dioxopyrrolidinyl)heptanoate The target compound was synthesized using ethyl heptanoate bromide as a raw material, in the same manner as in step b of Example 1.

[0190] Step c: Synthesis of (E)-7-(3-(3,4,5-trimethoxybenzylidene)-2,5-dioxopyrrolidinyl)-N-hydroxyheptylamide (E)-7-(3-(3,4,5-trimethoxybenzylidene)-2,5-dioxopyrrolidinyl)heptanoate ethyl was used as a starting material, and the target compound was synthesized in the same manner as in step c of Example 1. A white solid was obtained (yield 19.7%). 1H NMR (400 MHz, DMSO-d6) δ 10.33 (s, 1H), 8.65 (s, 1H), 7.43 (t, J = 2.4 Hz, 1H), 6.95 (s, 2H), 3.85 (s, 6H), 3.80 (d, J = 2.3 Hz, 2H), 3.71 (s, 3H), 3.48 (t, J = 7.1 Hz, 2H), 1.93 (t, J = 7.4 Hz, 2H), 1.59 - 1.43 (m, 4H), 1.31 - 1.20 (m, 4H). 13C NMR (101 MHz, DMSO) δ 174.89, 171.18, 169.52, 153.46, 139.44, 132.76, 130.11, 124.57, 108.23, 60.59, 56.46, 38.46, 33.85, 32.63, 28.62, 27.67, 26.45, 25.46.

[0191] (Example 36) (E)-7-(3-(4-hydroxy-3,5-dimethoxybenzylidene)-2,5-dioxopyrrolidinyl)-N-hydroxyheptylamide(I-36)

[0192] [ka]

[0193] Step a: Synthesis of (E)-3-(4-hydroxy-3,5-dimethoxybenzylidene)pyrrolidine-2,5-dione The target compound was synthesized using 4-hydroxy-3,5-dimethoxybenzaldehyde as a starting material, by the same method as in step a of Example 1.

[0194] Step b: Synthesis of (E)-7-(3-(4-hydroxy-3,5-dimethoxybenzylidene)-2,5-dioxopyrrolidinyl)heptanoate ethyl The target compound was synthesized using ethyl heptanoate bromide as a raw material, in the same manner as in step b of Example 1.

[0195] Step c: Synthesis of (E)-7-(3-(4-hydroxy-3,5-dimethoxybenzylidene)-2,5-dioxopyrrolidinyl)-N-hydroxyheptylamide (E)-7-(3-(4-hydroxy-3,5-dimethoxybenzylidene)-2,5-dioxopyrrolidinyl)heptanoate ethyl was used as a starting material, and the target compound was synthesized in the same manner as in step c of Example 1. A yellow solid was obtained (yield 13.1%). 1H NMR (400 MHz, DMSO-d6) δ 10.32 (s, 1H), 9.06 (s, 1H), 8.65 (s, 1H), 7.39 (s, 1H), 6.91 (s, 2H), 3.82 (s, 6H), 3.75 (s, 2H), 3.48 (d, J = 7.2 Hz, 2H), 1.92 (t, J = 7.3 Hz, 2H), 1.52 - 1.44 (m, 4H), 1.27 - 1.21 (m, 4H). 13C NMR (101 MHz, DMSO) δ 174.98, 171.35, 169.52, 148.46, 138.40, 133.48, 124.91, 122.02, 108.63, 56.51, 38.38, 33.93, 32.64, 28.62, 27.71, 26.45, 25.46.

[0196] (Example 37) (E)-7-(3-(2-hydroxybenzylidene)-2,5-dioxopyrrolidinyl)-N-hydroxyheptylamide(I-37)

[0197] [ka]

[0198] Step a: Synthesis of (E)-3-(2-hydroxybenzylidene)pyrrolidine-2,5-dione The target compound was synthesized using 2-hydroxybenzaldehyde as a raw material, by the same method as in step a of Example 1.

[0199] Step b: Synthesis of ethyl (E)-7-(3-(2-hydroxybenzylidene)-2,5-dioxopyrrolidinyl)heptanoate The target compound was synthesized using ethyl heptanoate bromide as a raw material, in the same manner as in step b of Example 1.

[0200] Step c: Synthesis of (E)-7-(3-(2-hydroxybenzylidene)-2,5-dioxopyrrolidinyl)-N-hydroxyheptylamide (E)-7-(3-(2-hydroxybenzylidene)-2,5-dioxopyrrolidinyl)heptanoate ethyl was used as a starting material, and the target compound was synthesized in the same manner as in step c of Example 1. A white solid was obtained (yield 21.2%). 1H NMR (400 MHz, DMSO-d6) δ 10.33 (s, 1H), 10.20 (s, 1H), 8.65 (s, 1H), 7.80 (t, J = 2.5 Hz, 1H), 7.49 (d, J = 7.9 Hz, 1H), 7.25 (t, J = 7.6 Hz, 1H), 6.94 (d, J = 8.1 Hz, 1H), 6.88 (t, J = 7.5 Hz, 1H), 3.65 (d, J = 2.7 Hz, 2H), 3.47 (t, J = 7.1 Hz, 2H), 1.93 (t, J = 7.3 Hz, 2H), 1.62 - 1.42 (m, 4H), 1.34 - 1.18 (m, 4H). 13C NMR (101 MHz, DMSO) δ 174.94, 171.38, 169.54, 157.51, 131.82, 129.56, 127.17, 123.88, 121.49, 119.87, 116.31, 38.41, 34.05, 32.64, 28.63, 27.70, 26.45, 25.45.

[0201] (Example 38) (E)-7-(3-(2-ethoxybenzylidene)-2,5-dioxopyrrolidinyl)-N-hydroxyheptylamide(I-38)

[0202] [ka]

[0203] Step a: Synthesis of (E)-3-(2-ethoxybenzylidene)pyrrolidine-2,5-dione The target compound was synthesized using 2-ethoxybenzaldehyde as a raw material, in the same manner as in step a of Example 1.

[0204] Step b: Synthesis of ethyl (E)-7-(3-(2-ethoxybenzylidene)-2,5-dioxopyrrolidinyl)heptanoate The target compound was synthesized using ethyl heptanoate bromide as a raw material, in the same manner as in step b of Example 1.

[0205] Step c: Synthesis of (E)-7-(3-(2-ethoxybenzylidene)-2,5-dioxopyrrolidinyl)-N-hydroxyheptylamide (E)-7-(3-(2-ethoxybenzylidene)-2,5-dioxopyrrolidinyl)heptanoate ethyl was used as a starting material, and the target compound was synthesized in the same manner as in step c of Example 1. A white solid was obtained (yield 12.5%). 1H NMR (300 MHz, DMSO-d6) δ 10.35 (s, 1H), 8.68 (s, 1H), 7.79 (t, J = 2.3 Hz, 1H), 7.57 (dd, J = 7.8, 1.6 Hz, 1H), 7.41 (ddd, J = 8.8, 7.4, 1.6 Hz, 1H), 7.10 (dd, J = 8.4, 1.0 Hz, 1H), 7.02 (t, J = 7.5 Hz, 1H), 4.13 (q, J = 6.9 Hz, 2H), 3.66 (d, J = 2.4 Hz, 2H), 3.47 (t, J = 7.1 Hz, 2H), 1.93 (t, J = 7.3 Hz, 2H), 1.55 - 1.44 (m, 4H), 1.38 (t, J = 6.9 Hz, 3H), 1.26 - 1.23 (m, 4H). 13C NMR (75 MHz, DMSO) δ 174.89, 171.25, 169.52, 157.82, 131.99, 129.62, 126.64, 125.13, 123.03, 121.03, 112.81, 64.23, 38.43, 34.00, 32.63, 28.63, 27.68, 26.44, 25.44, 15.07.

[0206] (Example 39) (E)-7-(3-(5-bromo-2-methoxybenzylidene)-2,5-dioxopyrrolidinyl)-N-hydroxyheptylamide(I-39)

[0207] [ka]

[0208] Step a: Synthesis of (E)-3-(5-bromo-2-methoxybenzylidene)pyrrolidine-2,5-dione The target compound was synthesized using 5-bromo-2-methoxybenzaldehyde as a starting material, by the same method as in step a of Example 1.

[0209] Step b: Synthesis of ethyl (E)-7-(3-(5-bromo-2-methoxybenzylidene)-2,5-dioxopyrrolidinyl)heptanoate The target compound was synthesized using ethyl heptanoate bromide as a raw material, in the same manner as in step b of Example 1.

[0210] Step c: Synthesis of (E)-7-(3-(5-bromo-2-methoxybenzylidene)-2,5-dioxopyrrolidinyl)-N-hydroxyheptylamide (E)-7-(3-(5-bromo-2-methoxybenzylidene)-2,5-dioxopyrrolidinyl)heptanoate ethyl was used as a starting material, and the target compound was synthesized in the same manner as in step c of Example 1. A white solid was obtained (yield 19.8%). 1H NMR (400 MHz, DMSO-d6) δ 10.33 (s, 1H), 8.65 (s, 1H), 7.65 (t, J = 2.4 Hz, 1H), 7.50 (d, J = 8.4 Hz, 1H), 7.33 (d, J = 1.9 Hz, 1H), 7.23 (dd, J = 8.3, 1.9 Hz, 1H), 3.90 (s, 3H), 3.63 (d, J = 2.5 Hz, 2H), 3.46 (t, J = 7.2 Hz, 2H), 1.93 (t, J = 7.4 Hz, 2H), 1.56 - 1.42 (m, 4H), 1.27 - 1.22 (m, 4H). 13C NMR (101 MHz, DMSO) δ 174.72, 171.06, 169.52, 159.07, 130.97, 126.17, 125.42, 124.82, 124.10, 122.34, 115.37, 56.79, 38.48, 33.96, 32.64, 28.62, 27.65, 26.43, 25.44.

[0211] (Example 40) (E)-7-(3-(4-bromo-2-methoxybenzylidene)-2,5-dioxopyrrolidinyl)-N-hydroxyheptylamide(I-40)

[0212] [ka]

[0213] Step a: Synthesis of (E)-3-(4-bromo-2-methoxybenzylidene)pyrrolidine-2,5-dione The target compound was synthesized using 4-bromo-2-methoxybenzaldehyde as a starting material, by the same method as in step a of Example 1.

[0214] Step b: Synthesis of ethyl (E)-7-(3-(4-bromo-2-methoxybenzylidene)-2,5-dioxopyrrolidinyl)heptanoate The target compound was synthesized using ethyl heptanoate bromide as a raw material, in the same manner as in step b of Example 1.

[0215] Step c: Synthesis of (E)-7-(3-(4-bromo-2-methoxybenzylidene)-2,5-dioxopyrrolidinyl)-N-hydroxyheptylamide (E)-7-(3-(4-bromo-2-methoxybenzylidene)-2,5-dioxopyrrolidinyl)heptanoate ethyl was used as a starting material, and the target compound was synthesized in the same manner as in step c of Example 1. A white solid was obtained (yield 18.6%). 1H NMR (400 MHz, DMSO-d6) δ 10.33 (s, 1H), 8.65 (s, 1H), 7.67 - 7.63 (m, 2H), 7.60 (dd, J = 8.8, 2.4 Hz, 1H), 7.10 (d, J = 8.9 Hz, 1H), 3.88 (s, 3H), 3.70 (d, J = 2.5 Hz, 2H), 3.47 (t, J = 7.2 Hz, 2H), 1.93 (t, J = 7.3 Hz, 2H), 1.56 - 1.42 (m, 4H), 1.29 - 1.19 (m, 4H). 13C NMR (101 MHz, DMSO) δ 174.70, 170.92, 169.52, 157.63, 134.22, 131.44, 127.04, 125.22, 125.12, 114.33, 112.73, 56.60, 38.50, 33.64, 32.64, 28.61, 27.64, 26.42, 25.44.

[0216] (Example 41) (E)-4-((3-benzylidene-2,5-dioxopyrrolidinyl)methyl)-N-hydroxybenzoylamide(I-41)

[0217] [ka]

[0218] Step a: Synthesis of (E)-3-benzylidenepyrrolidine-2,5-dione The operation and input amounts are the same as in step a of Example 1.

[0219] Step b: Synthesis of (E)-4-((3-benzylidene-2,5-dioxopyrrolidinyl)methyl)ethyl benzoate The target compound was synthesized using ethyl 4-(bromomethyl)benzoate as a raw material, by the same method as in step b of Example 1.

[0220] Step c: Synthesis of (E)-4-((3-benzylidene-2,5-dioxopyrrolidinyl)methyl)-N-hydroxybenzoylamide (E)-4-((3-benzylidene-2,5-dioxopyrrolidinyl)methyl)ethyl benzoate was used as a starting material, and the target compound was synthesized in the same manner as in step c of Example 1. A yellow solid was obtained (yield 11.3%). 1H NMR (400 MHz, DMSO-d6) δ 11.18 (s, 1H), 9.12 (s, 1H), 7.71 (d, J = 7.9 Hz, 2H), 7.67 (d, J = 7.0 Hz, 2H), 7.54 - 7.43 (m, 4H), 7.36 (d, J = 7.9 Hz, 2H), 4.74 (s, 2H), 3.82 (d, J = 2.3 Hz, 2H). 13C NMR (101 MHz, DMSO) δ 174.67, 170.98, 164.41, 139.79, 134.50, 132.98, 132.38, 130.77, 130.41, 129.49, 127.84, 127.56, 125.62, 41.69, 34.34

[0221] Pharmacological tests were performed on the compounds obtained in the above examples, and the following results were obtained.

[0222] (1) Measurement and results of the HDAC inhibitory activity of the target compound The inhibitory activity against HDAC1 was measured for the synthesized compounds using fluorescence resonance energy transfer (FRET), and compounds showing higher activity compared to the positive control drug were selected. HDAC1 was obtained by purification or using a commercially available reagent kit.

[0223] Specific method Enzymes were added to the reaction wells and reaction buffers to the control wells. Then, samples dissolved in DMSO were added to the reaction wells and incubated using a non-contact nanoliter ultrasonic dispensing system (Echo-550). A fluorescent substrate was added to each reaction well, and after rotational shaking, the mixture was sealed and incubated at 30°C for 1-2 hours. Subsequently, a chromogenic reagent containing TMP26 was added to stop the reaction and generate fluorescence. Fluorescence intensity was measured using an EnVision multimode microplate reader (PerkinElmer) (excitation light: 490 nm, fluorescence: 520 nm). After the color development stabilized, the endpoint value was read. The inhibition rate (%) compared to the DMSO control group was calculated using GraphPad Prism 4 for the obtained data.

[0224] [Table 1]

[0225] [Table 2]

[0226] (2) Measurement of the in vitro antitumor activity of the target compound The growth inhibitory effect of the compound on the following human tumor cell lines was evaluated using the MTT method. Specifically, the tests were conducted using human non-small cell lung cancer cell lines A549, NCI-H1650, human small cell lung cancer cell line H446, human prostate cancer cell lines DU145, PC-3, LNCaP, human colon cancer cell line HCT116, human breast cancer cell lines MDA-MB-231, and MCF-7.

[0227] Specific method Cells in the exponential growth phase were harvested, the number of viable cells was counted, and the concentration of the cell suspension was adjusted using the culture medium corresponding to each cell type. 100 μL of the cell suspension was added to each well of a 96-well cell culture plate and incubated at 37°C in a 5% CO2 incubator for 24 hours. The test compound was dissolved in DMSO to prepare a stock solution of the specified concentration, which was then diluted 500-fold with culture medium and added to each of the four-well rows. For each cell line, 100 μL of the 500-fold diluted solution was added to each well, resulting in a final DMSO concentration of 0.1%. 96 hours after drug treatment, 10 μL of PBS solution containing 5 mg / mL of MTT was added to each well and incubated at 37°C in a 5% CO2 incubator for 4 hours. Subsequently, the culture medium in the 96-well plate was removed, 150 μL of DMSO was added to each well to induce color development, and the absorbance was measured using a microplate reader. The median inhibition rate (%) compared to the DMSO control group was calculated using GraphPad Prism 4 for the obtained data.

[0228] [Table 3] TIFF2026523006000047.tif255166

[0229] [Table 4]

[0230] From the results of the above pharmacological tests, it has become clear that the compound represented by general formula I of the present invention and its pharmaceutically acceptable salts have excellent inhibitory activity against HDACs. Therefore, the compound represented by general formula I and its pharmaceutically acceptable salts can be used to treat clinical symptoms related to the above targets. Diseases related to HDACs include, but are not limited to, lung cancer, melanoma, liver cancer, kidney cancer, leukemia, non-small cell lung cancer, prostate cancer, thyroid cancer, skin cancer, pancreatic cancer, ovarian cancer, testicular cancer, breast cancer, bladder cancer, gallbladder cancer, myelodysplastic syndrome, lymphoma, esophageal cancer, follicular thyroid cancer, gastrointestinal cancer, tumors of the central or peripheral nervous system (e.g., astrocytoma, neuroblastoma, glioma or schwannoma), mesothelioma, type II diabetes mellitus (non-insulin-dependent diabetes mellitus), and autoimmune diseases.

[0231] The present invention is not limited to the embodiments described above, and other embodiments may also be included. Furthermore, technical means obtained by equivalent substitutions or equivalent modifications are also included within the scope of the claims of the present invention.

Claims

1. A compound represented by the following formula (I) or a pharmaceutically acceptable salt thereof. 【Chemistry 44】 (In the formula, X, Y, Z, M 1 M 2 Each of these independently represents a carbon atom or a nitrogen atom. X, Y, Z, M 1 M 2 If is a carbon atom, then each independently, R 2 It may be arbitrarily substituted with R 2 is hydrogen, alkyl group, cyano group, halogen, haloalkyl group, hydroxy group, mercapto group, alkoxy group, alkylamino group, alkylthio group, alkoxyalkyl group, arylalkyl group, diarylalkyl group, aryl group or Het. M 3 is carbon, each independently R 4 , R 5 may be optionally substituted with, R 4 , R 5 is hydrogen, deuterium, an alkyl group, a haloalkyl group, a hydroxy group, a mercapto group, an alkoxy group, an alkylamino group, an alkylthio group, an alkoxyalkyl group, methylene, an arylalkyl group, a diarylalkyl group, an aryl group or Het, Q 1 This is selected from saturated or unsaturated linear or branched hydrocarbon groups having 1 to 8 carbon atoms, aryl groups, or Het. R 1 is a hydroxyl group, one or more R 3 Selected from substituted 2-aminophenyl groups, R 3 is hydrogen, alkyl group, cyano group, halogen, haloalkyl group, hydroxyl group, mercapto group, alkoxy group, alkylthio group, alkoxyalkyl group, arylalkyl group, aryl group or Het, Alkyl groups are linear or branched saturated hydrocarbon groups having 1 to 6 carbon atoms, or cyclic saturated hydrocarbon groups having 3 to 6 carbon atoms, or cyclic saturated hydrocarbon groups having 3 to 6 carbon atoms bonded to linear or branched saturated hydrocarbon groups having 1 to 6 carbon atoms. An alkoxy group is a linear or branched saturated hydrocarbon group having 1 to 6 carbon atoms, or a cyclic saturated hydrocarbon group having 3 to 6 carbon atoms, or a cyclic saturated hydrocarbon group having 3 to 6 carbon atoms bonded to a linear or branched saturated hydrocarbon group having 1 to 6 carbon atoms, where each carbon atom may be optionally substituted with oxygen. The alkylamino group is a linear or branched saturated hydrocarbon group having 1 to 6 carbon atoms, or a cyclic saturated hydrocarbon group having 3 to 6 carbon atoms, or a cyclic saturated hydrocarbon group having 3 to 6 carbon atoms bonded to a linear or branched saturated hydrocarbon group having 1 to 6 carbon atoms, and each carbon atom may be optionally substituted with an NH group. An alkoxyalkyl group is a group formed by the bonding of an alkoxy group and an alkyl group as defined above. Alkenyl and alkynyl groups are linear or branched unsaturated hydrocarbon groups having 1 to 6 carbon atoms, and containing double or triple bonds. The aryl group is a carbon ring selected from a phenyl group, a naphthyl group, an acenaphthyl group, or a tetrahydronaphthyl group, each of which may be optionally substituted with one, two, or three substituents, each substituent independently selected from hydrogen, alkyl, cyano, halogen, haloalkyl, hydroxy, mercapto, alkoxy, alkylthio, alkoxyalkyl, arylalkyl, diarylalkyl, aryl, or Het. Arylalkyl groups and diarylalkyl groups are groups formed by bonding an aryl group and an alkyl group as defined above. Het is a monocyclic heterocycle selected from pyrrolyl, pyrazolyl, imidazolyl, furanyl, thienyl, oxazolyl, isoxazolyl, thiazolyl, isothiazolyl, pyridyl, pyrimidyl, pyrazinyl, or pyridadinyl group, or a quinolinyl, quinoxalinyl, indolyl, benzimidazolyl, benzoxazolyl, benzoisoxazolyl, benzothiazolyl, benzoisothiazolyl, benzofuranyl, benzothienyl, or 2,3-dihydrobenzo[1,4]di A bicyclic heterocycle selected from xacyclohexenyl or benzo[1,3]dioxacyclopentenyl, or a monocyclic saturated hydrocarbon group having 3 to 6 carbon atoms or a bicyclic saturated hydrocarbon group having 6 to 12 carbon atoms, wherein the carbon atoms on the ring may be independently and optionally replaced with 1 to 4 O, S, N, or NH atoms, and each monocyclic or dicyclic ring may be optionally substituted with 1, 2, or 3 substituents, each substituent independently selected from halogens, haloalkyls, hydroxyls, alkyls, or alkoxys. Halogens are substituents selected from fluorine, chlorine, bromine, or iodine. A haloalkyl group is a linear or branched saturated hydrocarbon group having 1 to 6 carbon atoms, a cyclic saturated hydrocarbon group having 3 to 6 carbon atoms, or a cyclic saturated hydrocarbon group having 3 to 6 carbon atoms bonded to a linear or branched saturated hydrocarbon group having 1 to 6 carbon atoms, and one or more carbon atoms may be substituted with one or more halogen atoms.

2. In the formula, X, Y, Z, M 1 M 2 Each of these independently represents a carbon atom or a nitrogen atom, and X, Y, Z, M 1 M 2 If each is a carbon atom, then R is independent of each other. 2 It may be arbitrarily substituted with R 2 These are hydrogen, alkyl groups, cyano groups, halogens, haloalkyl groups, alkoxy groups, alkylthio groups, and alkoxyalkyl groups. M 3 These are carbon atoms, and each is independently R 4 , R 5 It may be arbitrarily substituted with R 4 , R 5 is hydrogen, deuterium, alkyl group, haloalkyl group, hydroxyl group, mercapto group, alkoxy group, alkylamino group, alkylthio group, alkoxyalkyl group, methylene, arylalkyl group, diarylalkyl group, aryl group or Het, Q 1 This is selected from saturated or unsaturated linear or branched hydrocarbon groups and aryl groups having 1 to 8 carbon atoms. R 1 is a hydroxyl group, one or more R 3 Selected from substituted 2-aminophenyl groups, R 3 is hydrogen, alkyl group, cyano group, halogen, haloalkyl group, aryl group or Het. The compound according to claim 1, characterized in that it is a compound according to claim 1.

3. In the formula, X, Y, Z, M 1 M 2 Each of these independently represents a carbon atom or a nitrogen atom, and X, Y, Z, M 1 M 2 If each is a carbon atom, then R is independent of each other. 2 It may be arbitrarily substituted with R 2 These are hydrogen, alkyl, halogen, and alkoxy groups. M 3 These are carbon atoms, and each is independently R 4 , R 5 It may be arbitrarily substituted with R 4 , R 5 is hydrogen, deuterium, alkyl group, haloalkyl group, hydroxyl group, mercapto group, alkoxy group, alkylamino group, alkylthio group, alkoxyalkyl group, methylene, arylalkyl group, diarylalkyl group, aryl group or Het, Q 1 This is selected from saturated or unsaturated linear or branched hydrocarbon groups and aryl groups having 3 to 8 carbon atoms. R 1 is a hydroxyl group, one or more R 3 Selected from substituted 2-aminophenyl groups, R 3 is hydrogen, alkyl group, cyano group, halogen, haloalkyl group, aryl group or Het. The compound according to claim 1, characterized in that it is a compound according to claim 1.

4. (E)-4-(3-benzylidene-2,5-dioxopyrrolidinyl)-N-hydroxybutylamide (I-1), (E)-4-(3-benzylidene-2,5-dioxopyrrolidinyl)-N-hydroxypentylamide(I-2), (E)-4-(3-benzylidene-2,5-dioxopyrrolidinyl)-N-hydroxyhexylamide(I-3), (E)-4-(3-benzylidene-2,5-dioxopyrrolidinyl)-N-hydroxyheptylamide(I-4), (E)-4-(3-benzylidene-2,5-dioxopyrrolidinyl)-N-hydroxyoctylamide(I-5), (E)-N-(2-amino-4-fluorophenyl)-4-(3-benzylidene-2,5-dioxopyrrolidinyl)butylamide (I-6), (E)-N-(2-amino-4-fluorophenyl)-5-(3-benzylidene-2,5-dioxopyrrolidinyl)pentylamide (I-7), (E)-N-(2-amino-4-fluorophenyl)-6-(3-benzylidene-2,5-dioxopyrrolidinyl)hexylamide (I-8), (E)-N-(2-amino-4-fluorophenyl)-7-(3-benzylidene-2,5-dioxopyrrolidinyl)heptylamide (I-9), 4-(3-((E)-benzylidene)-2,5-dioxopyrrolidinyl)-N-((1S,2S)-2-hydroxycyclohexyl)butylamide(I-10), 5-(3-((E)-benzylidene)-2,5-dioxopyrrolidinyl)-N-((1S,2S)-2-hydroxycyclohexyl)pentylamide (I-11), 6-(3-((E)-benzylidene)-2,5-dioxopyrrolidinyl)-N-((1S,2S)-2-hydroxycyclohexyl)hexylamide(I-12), 7-(3-((E)-benzylidene)-2,5-dioxopyrrolidinyl)-N-((1S,2S)-2-hydroxycyclohexyl)heptylamide(I-13), 8-(3-((E)-benzylidene)-2,5-dioxopyrrolidinyl)-N-((1S,2S)-2-hydroxycyclohexyl)octylamide(I-14), (E)-7-(3-(4-isopropylbenzylidene)-2,5-dioxopyrrolidinyl)-N-hydroxyheptylamide (I-15), (E)-7-(3-(4-dimethylaminobenzylidene)-2,5-dioxopyrrolidinyl)-N-hydroxyheptylamide(I-16), (E)-7-(3-(4-trifluoromethylbenzylidene)-2,5-dioxopyrrolidinyl)-N-hydroxyheptylamide (I-17), (E)-7-(3-(4-methylbenzylidene)-2,5-dioxopyrrolidinyl)-N-hydroxyheptylamide (I-18), (E)-7-(3-(2-methylbenzylidene)-2,5-dioxopyrrolidinyl)-N-hydroxyheptylamide (I-19), (E)-7-(3-(2-cyanobenzylidene)-2,5-dioxopyrrolidinyl)-N-hydroxyheptylamide (I-20), (E)-7-(3-(2-pyridylmethylidene)-2,5-dioxopyrrolidinyl)-N-hydroxyheptylamide (I-21), (E)-7-(3-(2-naphthylmethylidene)-2,5-dioxopyrrolidinyl)-N-hydroxyheptylamide (I-22), (E)-7-(3-(2-thienylmethylidene)-2,5-dioxopyrrolidinyl)-N-hydroxyheptylamide (I-23), (E)-7-(3-(2-chlorobenzylidene)-2,5-dioxopyrrolidinyl)-N-hydroxyheptylamide (I-24), (E)-7-(3-(3-chlorobenzylidene)-2,5-dioxopyrrolidinyl)-N-hydroxyheptylamide (I-25), (E)-7-(3-(4-chlorobenzylidene)-2,5-dioxopyrrolidinyl)-N-hydroxyheptylamide (I-26), (E)-7-(3-(3-bromobenzylidene)-2,5-dioxopyrrolidinyl)-N-hydroxyheptylamide (I-27), (E)-7-(3-(3-fluorobenzylidene)-2,5-dioxopyrrolidinyl)-N-hydroxyheptylamide (I-28), (E)-7-(3-(3-iodobenzylidene)-2,5-dioxopyrrolidinyl)-N-hydroxyheptylamide (I-29), (E)-7-(3-(3,4-dichlorobenzylidene)-2,5-dioxopyrrolidinyl)-N-hydroxyheptylamide (I-30), (E)-7-(3-(2-methoxybenzylidene)-2,5-dioxopyrrolidinyl)-N-hydroxyheptylamide (I-31), (E)-7-(3-(3-methoxybenzylidene)-2,5-dioxopyrrolidinyl)-N-hydroxyheptylamide (I-32), (E)-7-(3-(4-methoxybenzylidene)-2,5-dioxopyrrolidinyl)-N-hydroxyheptylamide (I-33), (E)-7-(3-(3,4-dimethoxybenzylidene)-2,5-dioxopyrrolidinyl)-N-hydroxyheptylamide (I-34), (E)-7-(3-(3,4,5-trimethoxybenzylidene)-2,5-dioxopyrrolidinyl)-N-hydroxyheptylamide (I-35), (E)-7-(3-(4-hydroxy-3,5-dimethoxybenzylidene)-2,5-dioxopyrrolidinyl)-N-hydroxyheptylamide (I-36), (E)-7-(3-(2-hydroxybenzylidene)-2,5-dioxopyrrolidinyl)-N-hydroxyheptylamide (I-37), (E)-7-(3-(2-ethoxybenzylidene)-2,5-dioxopyrrolidinyl)-N-hydroxyheptylamide (I-38), (E)-7-(3-(5-bromo-2-methoxybenzylidene)-2,5-dioxopyrrolidinyl)-N-hydroxyheptylamide (I-39), (E)-7-(3-(4-bromo-2-methoxybenzylidene)-2,5-dioxopyrrolidinyl)-N-hydroxyheptylamide (I-40), (E)-4-((3-benzylidene-2,5-dioxopyrrolidinyl)methyl)-N-hydroxybenzoylamide (I-41) The compound according to claim 1, characterized in that it is a compound according to claim 1.

5. A pharmaceutical composition comprising a compound according to any one of claims 1 to 4 or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier, wherein the compound according to any one of claims 1 to 4 or a pharmaceutically acceptable salt thereof is an active ingredient.

6. Use of the compound according to any one of claims 1 to 4 in the preparation of a pharmaceutical product used for the prevention or treatment of clinical symptoms associated with HDACs.

7. The use of the compound according to claim 6 is characterized in that diseases associated with HDACs include lung cancer, melanoma, liver cancer, kidney cancer, leukemia, prostate cancer, thyroid cancer, skin diseases, pancreatic cancer, ovarian cancer, testicular cancer, breast cancer, bladder cancer, gallbladder cancer, myelodysplastic syndrome, lymphoma, esophageal cancer, gastrointestinal cancer, astrocytoma, neuroblastoma, glioma, schwannoma, mesothelioma, non-insulin-dependent diabetes mellitus, and autoimmune diseases.

Images